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Conserved domains on  [gi|2462619319|ref|XP_054216410|]
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inhibitor of nuclear factor kappa-B kinase subunit beta isoform X9 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
IKBKB_SDD pfam18397
IQBAL scaffold dimerization domain; This is the C-terminal scaffold dimerization domain (SDD) ...
 179-453 0e+00

IQBAL scaffold dimerization domain; This is the C-terminal scaffold dimerization domain (SDD) found in inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB (EC:2.7.11.10). IKK2 also known as IKBKB is one of the core component of IKB kinases (IKK). IKB kinase (IKK) is an enzyme that quickly becomes active in response to diverse stresses on a cell. The SDD consists primarily of two long alpha-helices.


:

Pssm-ID: 465745  Cd Length: 275  Bit Score: 516.96  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 179 LFDNSKITYETQISPRPQPESVSCILQEPKRNLAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKM 258
Cdd:pfam18397   1 LFDKSKTVYEGQFAPRPLPESVNYIVRDPKRQLPYSPLRKVWGQAWHYIRGLKEDYSRLQQGQRAAMLSLLRYNSNLSKM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 259 KNSMASMSQQLKAKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMALQTDIVDLQ 338
Cdd:pfam18397  81 KNEMFSMSQQLKAKLDFFKTSIQIDLEKYSEQMAFGISSEKMLSAWREMEQKAELCGQVAEVNKLDEEMMALQTDIVELQ 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 339 RSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPK 418
Cdd:pfam18397 161 RSPFARRQGEVLEDLEEKAIELYRQLREKPKDQRYSGDSTEMVRLILQTVQSQDKVVKELYTHLSKTLVCKQKILELLPK 240

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 2462619319 419 VEEVVSLMNEDEKTVVRLQEKRQKELWNLLKIACS 453
Cdd:pfam18397 241 VETVVSNIKEAEKTVVSMQEKRQKELWNLLKIACS 275
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 14-99 1.19e-48

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd14038:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 290  Bit Score: 171.30  E-value: 1.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319  14 SWGPCStWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCFKAL 93
Cdd:cd14038   206 NWQPVQ-WHGKVRQKSNEDIVVYEDLTGAVKFSSVLPTPNNLNGILAGKLERWLQCMLMWHPRQRGTDPPQNPNGCFQAL 284


                  ....*.
gi 2462619319  94 DDILNL 99
Cdd:cd14038   285 DSILNL 290
Ubl_IKKA_like cd17046
ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha ...
 100-180 3.87e-30

ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha and IKK-beta, and similar proteins; IKK, also termed IkappaB kinase, is an enzyme complex involved in propagating the cellular response to inflammation. It is part of the upstream nuclear factor kappa-B kinase (NF-kappaB) signal transduction cascade, and plays an important role in regulating the NF-kappaB transcription factor. IKK is composed of three subunits, IKK-alpha/CHUK, IKK-beta/IKBKB, and IKK-gamma/NEMO. The IKK-alpha and IKK-beta subunits together are catalytically active whereas the IKK-gamma subunit serves a regulatory function. IKK-alpha and IKK-beta phosphorylate the IkappaB proteins, marking them for degradation via ubiquitination and allowing NF-kappaB transcription factors to go into the nucleus. IKK-alpha, also known as IKK-A, or IkappaB kinase A (IkBKA), or conserved helix-loop-helix ubiquitous kinase (CHUK), or I-kappa-B kinase 1 (IKK1), or nuclear factor NF-kappa-B inhibitor kinase alpha (NFKBIKA), or transcription factor 16 (TCF-16), belongs to the serine/threonine protein kinase family. In addition to NF-kappaB response, it has many additional cellular targets in an NF-kappaB-independent manner. For instance, it plays a role in epidermal differentiation, as well as in the regulation of the cell cycle protein cyclin D1. IKK-beta, also known as IKK-B, or IkappaB kinase B (IkBKB), or I-kappa-B kinase 2 (IKK2), or nuclear factor NF-kappa-B inhibitor kinase beta (NFKBIKB), belongs to the serine/threonine protein kinase family as well. It interacts with many different protein partners and has been implicated in the treatment of many inflammatory diseases and cancers. Both IKK-alpha and IKK-beta contain an N-terminal catalytic domain followed by a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.


:

Pssm-ID: 340566  Cd Length: 75  Bit Score: 112.73  E-value: 3.87e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 100 KLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLALIPDKPATQCISdgklneGHTLDMDLVFL 179
Cdd:cd17046     1 KIVHIFNVTTYRILSYEVTEDTSLSTLQSWIERDTGIPVEDQELLLPTGVSLDPEKPASQCWL------VRGEDDYLVFL 74


                  .
gi 2462619319 180 F 180
Cdd:cd17046    75 F 75
IKKbetaNEMObind pfam12179
I-kappa-kinase-beta NEMO binding domain; This domain family is found in eukaryotes, and is ...
 496-525 1.98e-06

I-kappa-kinase-beta NEMO binding domain; This domain family is found in eukaryotes, and is approximately 40 amino acids in length. The family is found in association with pfam00069. These proteins are involved in inflammatory reactions. They cause release of NF-kappa-B into the nucleus of inflammatory cells and upregulation of transcription of proinflammatory cytokines. They perform this function by phosphorylating I-kappa-B proteins which are targeted for degradation to release NF-kappa-B. This kinase (I-kappa-kinase-beta) is found in association with IKK-alpha and NEMO (NF-kappa-B essential modulator). This domain is the binding site of IKK-beta for NEMO.


:

Pssm-ID: 463485  Cd Length: 37  Bit Score: 44.60  E-value: 1.98e-06
                          10        20        30
                  ....*....|....*....|....*....|
gi 2462619319 496 EELVAEAHNLCTLLENAIQDTVREQDQSFT 525
Cdd:pfam12179   1 AQLIEENLNYLSQLSSLMQEATKEQDQSLM 30
 
Name Accession Description Interval E-value
IKBKB_SDD pfam18397
IQBAL scaffold dimerization domain; This is the C-terminal scaffold dimerization domain (SDD) ...
 179-453 0e+00

IQBAL scaffold dimerization domain; This is the C-terminal scaffold dimerization domain (SDD) found in inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB (EC:2.7.11.10). IKK2 also known as IKBKB is one of the core component of IKB kinases (IKK). IKB kinase (IKK) is an enzyme that quickly becomes active in response to diverse stresses on a cell. The SDD consists primarily of two long alpha-helices.


Pssm-ID: 465745  Cd Length: 275  Bit Score: 516.96  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 179 LFDNSKITYETQISPRPQPESVSCILQEPKRNLAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKM 258
Cdd:pfam18397   1 LFDKSKTVYEGQFAPRPLPESVNYIVRDPKRQLPYSPLRKVWGQAWHYIRGLKEDYSRLQQGQRAAMLSLLRYNSNLSKM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 259 KNSMASMSQQLKAKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMALQTDIVDLQ 338
Cdd:pfam18397  81 KNEMFSMSQQLKAKLDFFKTSIQIDLEKYSEQMAFGISSEKMLSAWREMEQKAELCGQVAEVNKLDEEMMALQTDIVELQ 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 339 RSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPK 418
Cdd:pfam18397 161 RSPFARRQGEVLEDLEEKAIELYRQLREKPKDQRYSGDSTEMVRLILQTVQSQDKVVKELYTHLSKTLVCKQKILELLPK 240

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 2462619319 419 VEEVVSLMNEDEKTVVRLQEKRQKELWNLLKIACS 453
Cdd:pfam18397 241 VETVVSNIKEAEKTVVSMQEKRQKELWNLLKIACS 275
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 14-99 1.19e-48

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 171.30  E-value: 1.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319  14 SWGPCStWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCFKAL 93
Cdd:cd14038   206 NWQPVQ-WHGKVRQKSNEDIVVYEDLTGAVKFSSVLPTPNNLNGILAGKLERWLQCMLMWHPRQRGTDPPQNPNGCFQAL 284


                  ....*.
gi 2462619319  94 DDILNL 99
Cdd:cd14038   285 DSILNL 290
Ubl_IKKA_like cd17046
ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha ...
 100-180 3.87e-30

ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha and IKK-beta, and similar proteins; IKK, also termed IkappaB kinase, is an enzyme complex involved in propagating the cellular response to inflammation. It is part of the upstream nuclear factor kappa-B kinase (NF-kappaB) signal transduction cascade, and plays an important role in regulating the NF-kappaB transcription factor. IKK is composed of three subunits, IKK-alpha/CHUK, IKK-beta/IKBKB, and IKK-gamma/NEMO. The IKK-alpha and IKK-beta subunits together are catalytically active whereas the IKK-gamma subunit serves a regulatory function. IKK-alpha and IKK-beta phosphorylate the IkappaB proteins, marking them for degradation via ubiquitination and allowing NF-kappaB transcription factors to go into the nucleus. IKK-alpha, also known as IKK-A, or IkappaB kinase A (IkBKA), or conserved helix-loop-helix ubiquitous kinase (CHUK), or I-kappa-B kinase 1 (IKK1), or nuclear factor NF-kappa-B inhibitor kinase alpha (NFKBIKA), or transcription factor 16 (TCF-16), belongs to the serine/threonine protein kinase family. In addition to NF-kappaB response, it has many additional cellular targets in an NF-kappaB-independent manner. For instance, it plays a role in epidermal differentiation, as well as in the regulation of the cell cycle protein cyclin D1. IKK-beta, also known as IKK-B, or IkappaB kinase B (IkBKB), or I-kappa-B kinase 2 (IKK2), or nuclear factor NF-kappa-B inhibitor kinase beta (NFKBIKB), belongs to the serine/threonine protein kinase family as well. It interacts with many different protein partners and has been implicated in the treatment of many inflammatory diseases and cancers. Both IKK-alpha and IKK-beta contain an N-terminal catalytic domain followed by a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.


Pssm-ID: 340566  Cd Length: 75  Bit Score: 112.73  E-value: 3.87e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 100 KLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLALIPDKPATQCISdgklneGHTLDMDLVFL 179
Cdd:cd17046     1 KIVHIFNVTTYRILSYEVTEDTSLSTLQSWIERDTGIPVEDQELLLPTGVSLDPEKPASQCWL------VRGEDDYLVFL 74


                  .
gi 2462619319 180 F 180
Cdd:cd17046    75 F 75
IKKbetaNEMObind pfam12179
I-kappa-kinase-beta NEMO binding domain; This domain family is found in eukaryotes, and is ...
 496-525 1.98e-06

I-kappa-kinase-beta NEMO binding domain; This domain family is found in eukaryotes, and is approximately 40 amino acids in length. The family is found in association with pfam00069. These proteins are involved in inflammatory reactions. They cause release of NF-kappa-B into the nucleus of inflammatory cells and upregulation of transcription of proinflammatory cytokines. They perform this function by phosphorylating I-kappa-B proteins which are targeted for degradation to release NF-kappa-B. This kinase (I-kappa-kinase-beta) is found in association with IKK-alpha and NEMO (NF-kappa-B essential modulator). This domain is the binding site of IKK-beta for NEMO.


Pssm-ID: 463485  Cd Length: 37  Bit Score: 44.60  E-value: 1.98e-06
                          10        20        30
                  ....*....|....*....|....*....|
gi 2462619319 496 EELVAEAHNLCTLLENAIQDTVREQDQSFT 525
Cdd:pfam12179   1 AQLIEENLNYLSQLSSLMQEATKEQDQSLM 30
ubiquitin pfam00240
Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog) ...
 102-174 2.38e-03

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.


Pssm-ID: 459726 [Multi-domain]  Cd Length: 72  Bit Score: 36.77  E-value: 2.38e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462619319 102 VHILNMvTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQeAGLALIPDKPATQCisdgKLNEGHTLDM 174
Cdd:pfam00240   1 ITVKTL-DGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIY-SGKVLEDDQTLGEY----GIEDGSTIHL 67
UBQ smart00213
Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of ...
 110-174 8.13e-03

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression


Pssm-ID: 214563 [Multi-domain]  Cd Length: 72  Bit Score: 35.31  E-value: 8.13e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462619319  110 GTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQeAGLALIPDKPatqcISDGKLNEGHTLDM 174
Cdd:smart00213  10 GKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIY-KGKVLEDDRT----LADYGIQDGSTIHL 69
 
Name Accession Description Interval E-value
IKBKB_SDD pfam18397
IQBAL scaffold dimerization domain; This is the C-terminal scaffold dimerization domain (SDD) ...
 179-453 0e+00

IQBAL scaffold dimerization domain; This is the C-terminal scaffold dimerization domain (SDD) found in inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB (EC:2.7.11.10). IKK2 also known as IKBKB is one of the core component of IKB kinases (IKK). IKB kinase (IKK) is an enzyme that quickly becomes active in response to diverse stresses on a cell. The SDD consists primarily of two long alpha-helices.


Pssm-ID: 465745  Cd Length: 275  Bit Score: 516.96  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 179 LFDNSKITYETQISPRPQPESVSCILQEPKRNLAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKM 258
Cdd:pfam18397   1 LFDKSKTVYEGQFAPRPLPESVNYIVRDPKRQLPYSPLRKVWGQAWHYIRGLKEDYSRLQQGQRAAMLSLLRYNSNLSKM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 259 KNSMASMSQQLKAKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMALQTDIVDLQ 338
Cdd:pfam18397  81 KNEMFSMSQQLKAKLDFFKTSIQIDLEKYSEQMAFGISSEKMLSAWREMEQKAELCGQVAEVNKLDEEMMALQTDIVELQ 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 339 RSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPK 418
Cdd:pfam18397 161 RSPFARRQGEVLEDLEEKAIELYRQLREKPKDQRYSGDSTEMVRLILQTVQSQDKVVKELYTHLSKTLVCKQKILELLPK 240

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 2462619319 419 VEEVVSLMNEDEKTVVRLQEKRQKELWNLLKIACS 453
Cdd:pfam18397 241 VETVVSNIKEAEKTVVSMQEKRQKELWNLLKIACS 275
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 14-99 1.19e-48

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 171.30  E-value: 1.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319  14 SWGPCStWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCFKAL 93
Cdd:cd14038   206 NWQPVQ-WHGKVRQKSNEDIVVYEDLTGAVKFSSVLPTPNNLNGILAGKLERWLQCMLMWHPRQRGTDPPQNPNGCFQAL 284


                  ....*.
gi 2462619319  94 DDILNL 99
Cdd:cd14038   285 DSILNL 290
Ubl_IKKA_like cd17046
ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha ...
 100-180 3.87e-30

ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha and IKK-beta, and similar proteins; IKK, also termed IkappaB kinase, is an enzyme complex involved in propagating the cellular response to inflammation. It is part of the upstream nuclear factor kappa-B kinase (NF-kappaB) signal transduction cascade, and plays an important role in regulating the NF-kappaB transcription factor. IKK is composed of three subunits, IKK-alpha/CHUK, IKK-beta/IKBKB, and IKK-gamma/NEMO. The IKK-alpha and IKK-beta subunits together are catalytically active whereas the IKK-gamma subunit serves a regulatory function. IKK-alpha and IKK-beta phosphorylate the IkappaB proteins, marking them for degradation via ubiquitination and allowing NF-kappaB transcription factors to go into the nucleus. IKK-alpha, also known as IKK-A, or IkappaB kinase A (IkBKA), or conserved helix-loop-helix ubiquitous kinase (CHUK), or I-kappa-B kinase 1 (IKK1), or nuclear factor NF-kappa-B inhibitor kinase alpha (NFKBIKA), or transcription factor 16 (TCF-16), belongs to the serine/threonine protein kinase family. In addition to NF-kappaB response, it has many additional cellular targets in an NF-kappaB-independent manner. For instance, it plays a role in epidermal differentiation, as well as in the regulation of the cell cycle protein cyclin D1. IKK-beta, also known as IKK-B, or IkappaB kinase B (IkBKB), or I-kappa-B kinase 2 (IKK2), or nuclear factor NF-kappa-B inhibitor kinase beta (NFKBIKB), belongs to the serine/threonine protein kinase family as well. It interacts with many different protein partners and has been implicated in the treatment of many inflammatory diseases and cancers. Both IKK-alpha and IKK-beta contain an N-terminal catalytic domain followed by a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.


Pssm-ID: 340566  Cd Length: 75  Bit Score: 112.73  E-value: 3.87e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319 100 KLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLALIPDKPATQCISdgklneGHTLDMDLVFL 179
Cdd:cd17046     1 KIVHIFNVTTYRILSYEVTEDTSLSTLQSWIERDTGIPVEDQELLLPTGVSLDPEKPASQCWL------VRGEDDYLVFL 74


                  .
gi 2462619319 180 F 180
Cdd:cd17046    75 F 75
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 10-98 1.18e-27

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 112.93  E-value: 1.18e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319  10 FAHHSwgPCSTWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNgC 89
Cdd:cd13989   204 FLPNW--QPVQWHGKVKQKKPEHICAYEDLTGEVKFSSELPSPNHLSSILKEYLESWLQLMLRWDPRQRGGGPQNNPG-C 280


                  ....*....
gi 2462619319  90 FKALDDILN 98
Cdd:cd13989   281 FQLLDSILD 289
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 20-98 2.18e-23

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 100.38  E-value: 2.18e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462619319  20 TWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRG--TDPTYGPNGCFKALDDIL 97
Cdd:cd14039   209 TWHEKIKKKDPKHIFAVEEMNGEVRFSTHLPQPNNLCSLIVEPMEGWLQLMLNWDPVQRGggLDTDSKQPRCFVLMDQIL 288


                  .
gi 2462619319  98 N 98
Cdd:cd14039   289 S 289
IKKbetaNEMObind pfam12179
I-kappa-kinase-beta NEMO binding domain; This domain family is found in eukaryotes, and is ...
 496-525 1.98e-06

I-kappa-kinase-beta NEMO binding domain; This domain family is found in eukaryotes, and is approximately 40 amino acids in length. The family is found in association with pfam00069. These proteins are involved in inflammatory reactions. They cause release of NF-kappa-B into the nucleus of inflammatory cells and upregulation of transcription of proinflammatory cytokines. They perform this function by phosphorylating I-kappa-B proteins which are targeted for degradation to release NF-kappa-B. This kinase (I-kappa-kinase-beta) is found in association with IKK-alpha and NEMO (NF-kappa-B essential modulator). This domain is the binding site of IKK-beta for NEMO.


Pssm-ID: 463485  Cd Length: 37  Bit Score: 44.60  E-value: 1.98e-06
                          10        20        30
                  ....*....|....*....|....*....|
gi 2462619319 496 EELVAEAHNLCTLLENAIQDTVREQDQSFT 525
Cdd:pfam12179   1 AQLIEENLNYLSQLSSLMQEATKEQDQSLM 30
Ubl_ubiquitin_like cd17039
ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like ...
 106-174 3.48e-06

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.


Pssm-ID: 340559 [Multi-domain]  Cd Length: 68  Bit Score: 44.89  E-value: 3.48e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462619319 106 NMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQeAGLALIPDKPatqcISDGKLNEGHTLDM 174
Cdd:cd17039     4 KTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIY-NGKELKDDKT----LSDYGIKDGSTIHL 67
Ubl_FUBI cd01793
ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is ...
 110-175 1.91e-04

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.


Pssm-ID: 340491  Cd Length: 74  Bit Score: 39.96  E-value: 1.91e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462619319 110 GTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQeAGLALIPDKPATQCIsdgkLNEGHTLDMD 175
Cdd:cd01793     8 QSLHTLEVSGNETVADIKAHIAALEGIAVEDQVLLY-AGAPLEDDVVLGQCG----IPDLATLEVA 68
ubiquitin pfam00240
Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog) ...
 102-174 2.38e-03

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.


Pssm-ID: 459726 [Multi-domain]  Cd Length: 72  Bit Score: 36.77  E-value: 2.38e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462619319 102 VHILNMvTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQeAGLALIPDKPATQCisdgKLNEGHTLDM 174
Cdd:pfam00240   1 ITVKTL-DGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIY-SGKVLEDDQTLGEY----GIEDGSTIHL 67
Ubl_TBK1_like cd12219
ubiquitin-like (Ubl) domain found in non-canonical Inhibitor of kappa B kinases IKKepsilon and ...
 100-144 6.05e-03

ubiquitin-like (Ubl) domain found in non-canonical Inhibitor of kappa B kinases IKKepsilon and TBK1, and similar proteins; IKKepsilon and TBK1 (TRAF family member-associated NF-kappaB activator-binding kinase 1) are non-canonical members of IKK family. They have been characterized as activators of nuclear factor-kappaB (NF-kappaB), but they are not essential for NF-kappaB activation. They play critical roles in antiviral response via phosphorylation and activation of transcription factors IRF3, IRF7, STAT1 and STAT3. They are also involved in the survival, tumorigenesis and development of various cancers. Both IKKepsilon and TBK1 contain an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.


Pssm-ID: 340518  Cd Length: 77  Bit Score: 36.06  E-value: 6.05e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2462619319 100 KLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELL 144
Cdd:cd12219     2 KVIHVFSVSTCELLKIYLDPTETLAEFQELIAEQTEIPAKNQLLL 46
UBQ smart00213
Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of ...
 110-174 8.13e-03

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression


Pssm-ID: 214563 [Multi-domain]  Cd Length: 72  Bit Score: 35.31  E-value: 8.13e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462619319  110 GTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQeAGLALIPDKPatqcISDGKLNEGHTLDM 174
Cdd:smart00213  10 GKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIY-KGKVLEDDRT----LADYGIQDGSTIHL 69
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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