(data stored in ACNUC26462 zone)

HOGENOM: RAT18_PE176

ID   RAT18_PE176                          STANDARD;      PRT;   474 AA.
AC   RAT18_PE176; P13234; A1A5L5; Q63892;
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;AltName:
DE   Full=Calspermin; (RAT18.PE176).
GN   Name=Camk4;
OS   RATTUS NORVEGICUS.
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS RAT18.PE176.
CC       Rattus norvegicus chromosome 18 RGSC3.4  sequence 1..87265094
CC       annotated by Ensembl
CC   -!- ANNOTATIONS ORIGIN:KCC4_RAT
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 (By
CC       similarity).
CC   -!- FUNCTION: Calspermin (isoform 2) is a heat-stable, acidic,
CC       calmodulin-binding protein.
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-196
CC       within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of
CC       Thr-196 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-11 and Ser-12 is
CC       required for full activation. Inactivated by protein phosphatase
CC       2A (PPP2CA/PPP2CB) which dephosphorylates Thr-196, thereby
CC       terminating autonomous activity and helping to maintain the enzyme
CC       in its autoinhibited state (By similarity).
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 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in
CC       hippocampal neuron nuclei (By similarity). In spermatids,
CC       associated with chromatin and nuclear matrix (By similarity).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Calcium-calmodulin-dependent protein kinase type
CC       IV, Beta;
CC         IsoId=P13234-1; Sequence=Displayed;
CC       Name=2; Synonyms=Calspermin, Testis-specific;
CC         IsoId=P13234-2; Sequence=VSP_004789;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is expressed in brain and isoform 2
CC       is testis specific.
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 (By similarity).
CC   -!- PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-196.
CC       Dephosphorylated by protein phosphatase 2A. Autophosphorylated on
CC       Ser-11 and Ser-12 (By similarity).
CC   -!- PTM: Glycosylation at Ser-185 modulates the phosphorylation of
CC       CaMK4 at Thr-196 and negatively regulates its activity toward
CC       CREB1 in basal conditions and during early inomycin stimulation
CC       (By similarity).
CC   -!- PTM: The N-terminus of calspermin is blocked.
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=AAB28372.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC   -!- GENE_FAMILY: HOG000233016 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Rattus_norvegicus;ENSRNOG00000020478;ENSRNOT00000027771;ENSRNOP00000027771.
DR   EMBL; BC128706; - ;
DR   EMBL; J04446; - ;
DR   EMBL; J04600; - ;
DR   EMBL; L16999; - ;
DR   EMBL; M63334; - ;
DR   EMBL; M64757; - ;
DR   EMBL; M74488; - ;
DR   EMBL; S65840; - ;
DR   UniProtKB/Swiss-Prot; P13234; A1A5L5; Q63892; -.
DR   EMBL; M63334; AAA40865.1; -; mRNA.
DR   EMBL; M74488; AAA40845.1; -; Genomic_DNA.
DR   EMBL; M64757; AAA40856.1; -; mRNA.
DR   EMBL; M64757; AAA40857.1; -; mRNA.
DR   EMBL; S65840; AAB28372.1; ALT_INIT; mRNA.
DR   EMBL; BC128706; AAI28707.1; -; mRNA.
DR   EMBL; J04600; AAA41867.1; -; mRNA.
DR   EMBL; J04446; AAA40990.1; -; mRNA.
DR   IPI; IPI00230883; -.
DR   IPI; IPI00231822; -.
DR   PIR; A41103; TVRTC4.
DR   PIR; I52637; I52637.
DR   RefSeq; NP_036859.2; NM_012727.3.
DR   UniGene; Rn.11046; -.
DR   ProteinModelPortal; P13234; -.
DR   STRING; P13234; -.
DR   PhosphoSite; P13234; -.
DR   PRIDE; P13234; -.
DR   Ensembl; ENSRNOT00000027771; ENSRNOP00000027771; ENSRNOG00000020478.
DR   Ensembl; ENSRNOT00000042172; ENSRNOP00000049484; ENSRNOG00000020478.
DR   GeneID; 25050; -.
DR   KEGG; rno:25050; -.
DR   UCSC; M64757; rat.
DR   UCSC; NM_012727; rat.
DR   CTD; 814; -.
DR   RGD; 2264; Camk4.
DR   eggNOG; roNOG13085; -.
DR   InParanoid; P13234; -.
DR   OMA; TVPSCSA; -.
DR   OrthoDB; EOG4PNXH1; -.
DR   PhylomeDB; P13234; -.
DR   BRENDA; 2.7.11.17; 5301.
DR   NextBio; 605240; -.
DR   ArrayExpress; P13234; -.
DR   Genevestigator; P13234; -.
DR   GermOnline; ENSRNOG00000020478; Rattus norvegicus.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IDA:RGD.
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; RAT18.PE176; -.
KW   ENSRNOG00000020478820036002503210000011;
KW   Camk4; KCC4_RAT; Q6LED8_RAT; BC128706; J04446; J04600; L16999; M63334;
KW   M74488; S65840;
KW   Acetylation; Adaptive immunity; Alternative promoter usage;
KW   Alternative splicing; ATP-binding; Calcium; Calmodulin-binding;
KW   Complete proteome; Cytoplasm; Direct protein sequencing; Glycoprotein;
KW   Immunity; Inflammatory response; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
SQ   SEQUENCE   474 AA;  UNKNOWN MW;  UNKNOWN CRC64;
     MLKVTVPSCP SSPCSSVTSS TENLVPDYWI DGSKRDPLSD FFEVESELGR GATSIVYRCK
     QKGTQKPYAL KVLKKTVDKK IVRTEIGVLL RLSHPNIIKL KEIFETPTEI SLVLELVTGG
     ELFDRIVEKG YYSERDAADA VKQILEAVAY LHENGIVHRD LKPENLLYAT PAPDAPLKIA
     DFGLSKIVEH QVLMKTVCGT PGYCAPEILR GCAYGPEVDM WSVGIITYIL LCGFEPFYDE
     RGDQFMFRRI LNCEYYFISP WWDEVSLNAK DLVKKLIVLD PKKRLTTFQA LQHPWVTGKA
     ANFVHMDTAQ KKLQEFNARR KLKAAVKAVV ASSRLGSASS SHTNIQESNK ASSEAQPAQD
     GKDKTDPLEN KMQAGDHEAA KAAADETMKL QSEEVEEEEG VKEEEEEEEE EEETSRMVPQ
     EPEDRLETDD QEMKRNSEET LKSVEEEMDP KAEEEAAAVG LGVPPQQDAI LPEY
//

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