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Details on Person UniProt:Q99558 MAP3K14

Class:IdReferenceGeneProduct:58907
_chainChangeLogchain:1-947 added on Fri February 6 2015
_displayNameUniProt:Q99558 MAP3K14
_timestamp2025-02-21 18:38:33
chainchain:1-947
checksumC9D10F67FF7F48AC
commentFUNCTION Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Phosphorylates CHUK/IKKA, thereby promoting proteolytic processing of NFKB2/P100, which leads to NF-kappa-B activation via the non-canonical pathway (PubMed:25406581, PubMed:29230214). Has an essential role in the non-canonical NF-kappa-B signaling that regulates genes encoding molecules involved in B-cell survival, lymphoid organogenesis, and immune response (PubMed:25406581). Could act in a receptor-selective manner.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)SUBUNIT Interacts with TRAF2, TRAF5, TRAF6, IKKA and NFKB2/P100 (By similarity). Interacts with TRAF3 and PELI3. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with ZFP91. Interacts with NLRP12; this interaction promotes proteasomal degradation of MAP3K14. Directly interacts with DDX3X (PubMed:30341167). Interacts (via C-terminus and kinase domain) with PPPC3A (via N-terminus) and PPP3CB (By similarity).INTERACTION Weakly expressed in testis, small intestine, spleen, thymus, peripheral blood leukocytes, prostate, ovary and colon.PTM Autophosphorylated. Phosphorylation at Thr-559 is required to activate its kinase activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization.PTM Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. 'Lys-48'-linked polyubiquitination leads to its degradation by the proteasome, while 'Lys-63'-linked polyubiquitination stabilizes and activates it.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
descriptionrecommendedName: fullName evidence="22"Mitogen-activated protein kinase kinase kinase 14 ecNumber: 2.7.11.25 alternativeName: fullName evidence="19"NF-kappa-beta-inducing kinase shortName evidence="22"HsNIK alternativeName: fullName evidence="20"Serine/threonine-protein kinase NIK
geneNameMAP3K14
NIK
identifierQ99558
isSequenceChangedFALSE
keyword3D-structure
ATP-binding
Cytoplasm
Disease variant
Kinase
Nucleotide-binding
Phosphoprotein
Proteomics identification
Reference proteome
Serine/threonine-protein kinase
Transferase
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9909836] Weiser, Joel, 2024-05-14
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameMAP3K14
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:9002450] ENSEMBL:ENSG00000006062 MAP3K14 [Homo sapiens]
secondaryIdentifierM3K14_HUMAN
A8K2D8
D3DX67
Q8IYN1
sequenceLength947
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:168187] p-MAP3K14 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:168189] MAP3K14 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:5607646] Active NIK [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:5668525] K48polyUb-NIK [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:5668531] p-T559-MAP3K14 [cytosol] [Homo sapiens]
(referenceSequence)[ModifiedResidue:168368] phosphorylated residue at unknown position
[ModifiedResidue:5668523] O-phospho-L-threonine at 559
[GroupModifiedResidue:5668538] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position
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