(data stored in ACNUC26462 zone)

HOGENOM: HS5_PE1846

ID   HS5_PE1846                           STANDARD;      PRT;   473 AA.
AC   HS5_PE1846; Q16566; D3DSZ7;
DT   00-JAN-0000 (Rel. 1, Created)
DT   00-JAN-0000 (Rel. 2, Last sequence update)
DT   00-JAN-0000 (Rel. 3, Last annotation update)
DE   RecName: Full=Calcium/calmodulin-dependent protein kinase type IV;
DE   Short=CaMK IV; EC=2.7.11 17;AltName: Full=CaM kinase-GR; (HS5.PE1846).
GN   Name=CAMK4; Synonyms=CAMK, CAMK-GR, CAMKIV;
OS   HOMO SAPIENS.
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC   Hominoidea; Hominidae; Homininae; Homo.
OX   NCBI_TaxID=9606;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS5.PE1846.
CC       Homo sapiens chromosome 5 GRCh37  sequence 1..180905260 annotated by
CC       Ensembl
CC   -!- ANNOTATIONS ORIGIN:KCC4_HUMAN
CC   -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that
CC       operates in the calcium-triggered CaMKK-CaMK4 signaling cascade
CC       and regulates, mainly by phosphorylation, the activity of several
CC       transcription activators, such as CREB1, MEF2D, JUN and RORA,
CC       which play pivotal roles in immune response, inflammation, and
CC       memory consodilation. In the thymus, regulates the CD4(+)/CD8(+)
CC       double positive thymocytes selection threshold during T-cell
CC       ontogeny. In CD4 memory T-cells, is required to link T-cell
CC       antigen receptor (TCR) signaling to the production of IL2, IFNG
CC       and IL4 (through the regulation of CREB and MEF2). Regulates the
CC       differentiation and survival phases of osteolclasts and dendritic
CC       cells (DCs). Mediates DCs survival by linking TLR4 and the
CC       regulation of temporal expression of BCL2. Phosphrylates the
CC       transcription activator CREB1 on 'Ser-133' in hippocampal neuron
CC       nuclei and contribute to memory consolidation and long term
CC       potentiation (LTP) in the hippocampus. Can activate the MAP
CC       kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate
CC       transcription through the phosphorylation of ELK1 and ATF2. Can
CC       also phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC   -!- ENZYME REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC       calmodulin results in conformational change that relieves
CC       intrasteric autoinhibition and allows phosphorylation of Thr-200
CC       within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of
CC       Thr-200 results in a 10-20-fold increase in total activity to
CC       generate Ca(2+)/calmodulin-independent activity.
CC       Autophosphorylation of the N-terminus Ser-12 and Ser-13 is
CC       required for full activation. Inactivated by protein phosphatase
CC       2A (PPP2CA/PPP2CB) which dephosphorylates Thr-200, thereby
CC       terminating autonomous activity and helping to maintain the enzyme
CC       in its autoinhibited state.
CC   -!- SUBUNIT: Monomer (By similarity). Interacts with protein
CC       phosphatase 2A (PPP2CA/PPP2CB); the interaction is mutually
CC       exclusive with binding to Ca(2+)/calmodulin.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in
CC       hippocampal neuron nuclei. In spermatids, associated with
CC       chromatin and nuclear matrix (By similarity).
CC   -!- TISSUE SPECIFICITY: Expressed in brain, thymus, CD4 T-cells,
CC       testis and epithelial ovarian cancer tissue.
CC   -!- DEVELOPMENTAL STAGE: Expressed during differentiation of monocyte-
CC       derived dendritic cells (at protein level).
CC   -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin
CC       binding region and interacts in the inactive folded state with the
CC       catalytic domain as a pseudosubstrate.
CC   -!- PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-200.
CC       Dephosphorylated by protein phosphatase 2A. Autophosphorylated on
CC       Ser-12 and Ser-13.
CC   -!- PTM: Glycosylation at Ser-189 modulates the phosphorylation of
CC       CaMK4 at Thr-200 and negatively regulates its activity toward
CC       CREB1 in basal conditions and during early inomycin stimulation.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC       Ser/Thr protein kinase family. CaMK subfamily.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH16695.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC   -!- GENE_FAMILY: HOG000233016 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Homo_sapiens;ENSG00000152495;ENST00000282356;ENSP00000282356.
DR   EMBL; AC010275; - ;
DR   EMBL; AC010468; - ;
DR   EMBL; AC011422; - ;
DR   EMBL; AK312840; - ;
DR   EMBL; BC016695; - ;
DR   EMBL; BC025687; - ;
DR   EMBL; CH471086; - ;
DR   EMBL; D30742; - ;
DR   EMBL; L17000; - ;
DR   EMBL; L24959; - ;
DR   UniProtKB/Swiss-Prot; Q16566; D3DSZ7; -.
DR   EMBL; D30742; BAA06403.1; -; mRNA.
DR   EMBL; L17000; AAA35639.1; -; mRNA.
DR   EMBL; L24959; AAA18251.1; -; mRNA.
DR   EMBL; CH471086; EAW49033.1; -; Genomic_DNA.
DR   EMBL; CH471086; EAW49034.1; -; Genomic_DNA.
DR   EMBL; BC016695; AAH16695.2; ALT_INIT; mRNA.
DR   EMBL; BC025687; AAH25687.1; -; mRNA.
DR   IPI; IPI00430411; -.
DR   PIR; A53036; A53036.
DR   RefSeq; NP_001735.1; NM_001744.4.
DR   UniGene; Hs.591269; -.
DR   PDB; 2W4O; X-ray; 2.17 A; A=15-340.
DR   PDBsum; 2W4O; -.
DR   ProteinModelPortal; Q16566; -.
DR   SMR; Q16566; 28-429.
DR   STRING; Q16566; -.
DR   PhosphoSite; Q16566; -.
DR   PeptideAtlas; Q16566; -.
DR   PRIDE; Q16566; -.
DR   Ensembl; ENST00000282356; ENSP00000282356; ENSG00000152495.
DR   GeneID; 814; -.
DR   KEGG; hsa:814; -.
DR   UCSC; uc003kpf.1; human.
DR   CTD; 814; -.
DR   GeneCards; GC05P105739; -.
DR   H-InvDB; HIX0005080; -.
DR   HGNC; HGNC:1464; CAMK4.
DR   HPA; CAB004347; -.
DR   HPA; HPA011753; -.
DR   HPA; HPA017206; -.
DR   MIM; 114080; gene.
DR   neXtProt; NX_Q16566; -.
DR   PharmGKB; PA26050; -.
DR   eggNOG; prNOG13858; -.
DR   GeneTree; ENSGT00550000074354; -.
DR   InParanoid; Q16566; -.
DR   OMA; TVPSCSA; -.
DR   PhylomeDB; Q16566; -.
DR   BRENDA; 2.7.11.17; 2681.
DR   Pathway_Interaction_DB; nfat_3pathway; Role of Calcineurin-dependent NFAT signaling in lymphocytes.
DR   Pathway_Interaction_DB; hdac_classii_pathway; Signaling events mediated by HDAC Class II.
DR   Pathway_Interaction_DB; pi3kplctrkpathway; Trk receptor signaling mediated by PI3K and PLC-gamma.
DR   Reactome; REACT_11061; Signalling by NGF.
DR   Reactome; REACT_13685; Synaptic Transmission.
DR   Reactome; REACT_15295; Opioid Signalling.
DR   NextBio; 3300; -.
DR   PMAP-CutDB; Q16566; -.
DR   ArrayExpress; Q16566; -.
DR   Bgee; Q16566; -.
DR   CleanEx; HS_CAMK4; -.
DR   Genevestigator; Q16566; -.
DR   GermOnline; ENSG00000152495; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; EXP:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; EXP:Reactome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:EC.
DR   GO; GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
DR   GO; GO:0048011; P:nerve growth factor receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_cat_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR017442; Se/Thr_kinase-like_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR002290; Ser/Thr_kinase_dom.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Kinase_like; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   HOGENOMDNA; HS5.PE1846; -.
KW   ENSG000001524951755old_1320000031; ENSP000002823567901old_1320000031;
KW   B2R747_HUMAN; D3DSZ7_HUMAN; D6RE65_HUMAN; AC010275; AC010468; AC011422;
KW   BC016695; BC025687; CH471086; D30742; L17000; L24959;
KW   3D-structure; Acetylation; Adaptive immunity; ATP-binding; Calcium;
KW   Calmodulin-binding; Complete proteome; Cytoplasm; Glycoprotein;
KW   Immunity; Inflammatory response; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase.
SQ   SEQUENCE   473 AA;  UNKNOWN MW;  UNKNOWN CRC64;
     MLKVTVPSCS ASSCSSVTAS AAPGTASLVP DYWIDGSNRD ALSDFFEVES ELGRGATSIV
     YRCKQKGTQK PYALKVLKKT VDKKIVRTEI GVLLRLSHPN IIKLKEIFET PTEISLVLEL
     VTGGELFDRI VEKGYYSERD AADAVKQILE AVAYLHENGI VHRDLKPENL LYATPAPDAP
     LKIADFGLSK IVEHQVLMKT VCGTPGYCAP EILRGCAYGP EVDMWSVGII TYILLCGFEP
     FYDERGDQFM FRRILNCEYY FISPWWDEVS LNAKDLVRKL IVLDPKKRLT TFQALQHPWV
     TGKAANFVHM DTAQKKLQEF NARRKLKAAV KAVVASSRLG SASSSHGSIQ ESHKASRDPS
     PIQDGNEDMK AIPEGEKIQG DGAQAAVKGA QAELMKVQAL EKVKGADINA EEAPKMVPKA
     VEDGIKVADL ELEEGLAEEK LKTVEEAAAP REGQGSSAVG FEVPQQDVIL PEY
//

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