P12277 · KCRB_HUMAN
- ProteinCreatine kinase B-type
- GeneCKB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids381 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255).
Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity).
During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity).
Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity).
During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity).
Catalytic activity
- ATP + creatine = ADP + H+ + N-phosphocreatineThis reaction proceeds in the forward direction.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 72 | creatine (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 128-132 | ATP (UniProtKB | ChEBI) | ||||
Sequence: SSRVR | ||||||
Binding site | 130 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 132 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 191 | ATP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 232 | creatine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 236 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 285 | creatine (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 292 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 320 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 320-325 | ATP (UniProtKB | ChEBI) | ||||
Sequence: RGTGGV | ||||||
Binding site | 335 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular space | |
Cellular Component | mitochondrion | |
Cellular Component | plasma membrane | |
Molecular Function | ATP binding | |
Molecular Function | creatine kinase activity | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | futile creatine cycle | |
Biological Process | phosphocreatine biosynthetic process | |
Biological Process | substantia nigra development |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCreatine kinase B-type
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP12277
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to the mitochondria of thermogenic fat cells via the internal MTS-like signal (iMTS-L) region.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_025838 | 177 | in dbSNP:rs36002620 | |||
Sequence: K → R | ||||||
Mutagenesis | 283 | Complete loss of activity. | ||||
Sequence: C → S or Y | ||||||
Mutagenesis | 292 | Complete loss of activity. | ||||
Sequence: R → H, L, or Q | ||||||
Mutagenesis | 292 | 42% of wild-type activity. | ||||
Sequence: R → K | ||||||
Natural variant | VAR_025839 | 309 | in dbSNP:rs35156510 | |||
Sequence: S → L | ||||||
Mutagenesis | 340 | No change in activity. | ||||
Sequence: D → E | ||||||
Natural variant | VAR_049674 | 360 | in dbSNP:rs12505 | |||
Sequence: L → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 386 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Chain | PRO_0000211966 | 2-381 | UniProt | Creatine kinase B-type | |||
Sequence: PFSNSHNALKLRFPAEDEFPDLSAHNNHMAKVLTPELYAELRAKSTPSGFTLDDVIQTGVDNPGHPYIMTVGCVAGDEESYEVFKDLFDPIIEDRHGGYKPSDEHKTDLNPDNLQGGDDLDPNYVLSSRVRTGRSIRGFCLPPHCSRGERRAIEKLAVEALSSLDGDLAGRYYALKSMTEAEQQQLIDDHFLFDKPVSPLLLASGMARDWPDARGIWHNDNKTFLVWVNEEDHLRVISMQKGGNMKEVFTRFCTGLTQIETLFKSKDYEFMWNPHLGYILTCPSNLGTGLRAGVHIKLPNLGKHEKFSEVLKRLRLQKRGTGGVDTAAVGGVFDVSNADRLGFSEVELVQMVVDGVKLLIEMEQRLEQGQAIDDLMPAQK | |||||||
Modified residue | 4 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 4 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 6 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 35 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 35 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 39 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Cross-link | 45 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 101 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 107 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue | 125 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 125 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 163 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 164 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 178 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 199 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 199 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 269 | UniProt | 3'-nitrotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 309 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 309 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 322 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 322 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 337 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 381 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K |
Post-translational modification
Ubiquitinated by the ECS(ASB9) complex, leading to its degradation by the proteasome.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Dimer of identical or non-identical chains, which can be either B (brain type) or M (muscle type). With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain. Interacts with SLC12A6 (via C-terminus); the interaction may be required for SLC12A6 potassium-chloride cotransport activity (PubMed:18566107).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P12277 | ASB9 Q96DX5 | 12 | EBI-357706, EBI-745641 | |
BINARY | P12277 | CKM P06732 | 3 | EBI-357706, EBI-4287089 | |
BINARY | P12277 | CUL3 Q13618 | 3 | EBI-357706, EBI-456129 | |
XENO | P12277 | PRO_0000278738 Q03463 | 3 | EBI-357706, EBI-9081620 | |
BINARY | P12277 | TCF4 P15884 | 2 | EBI-357706, EBI-533224 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 11-98 | Phosphagen kinase N-terminal | ||||
Sequence: KLRFPAEDEFPDLSAHNNHMAKVLTPELYAELRAKSTPSGFTLDDVIQTGVDNPGHPYIMTVGCVAGDEESYEVFKDLFDPIIEDRHG | ||||||
Compositional bias | 96-113 | Basic and acidic residues | ||||
Sequence: RHGGYKPSDEHKTDLNPD | ||||||
Region | 96-122 | Disordered | ||||
Sequence: RHGGYKPSDEHKTDLNPDNLQGGDDLD | ||||||
Domain | 125-367 | Phosphagen kinase C-terminal | ||||
Sequence: YVLSSRVRTGRSIRGFCLPPHCSRGERRAIEKLAVEALSSLDGDLAGRYYALKSMTEAEQQQLIDDHFLFDKPVSPLLLASGMARDWPDARGIWHNDNKTFLVWVNEEDHLRVISMQKGGNMKEVFTRFCTGLTQIETLFKSKDYEFMWNPHLGYILTCPSNLGTGLRAGVHIKLPNLGKHEKFSEVLKRLRLQKRGTGGVDTAAVGGVFDVSNADRLGFSEVELVQMVVDGVKLLIEMEQRL | ||||||
Region | 130-138 | Internal MTS-like signal | ||||
Sequence: RVRTGRSIR |
Domain
The internal MTS-like signal (iMTS-L) mediates targeting to mitochondria thermogenic fat cells.
Sequence similarities
Belongs to the ATP:guanido phosphotransferase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length381
- Mass (Da)42,644
- Last updated1989-10-01 v1
- Checksum637AA67A86AE3059
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 41-42 | in Ref. 1; AAA76851 | ||||
Sequence: EL → DV | ||||||
Sequence conflict | 78 | in Ref. 3; AAA76850 and 10; AAA52024 | ||||
Sequence: D → G | ||||||
Compositional bias | 96-113 | Basic and acidic residues | ||||
Sequence: RHGGYKPSDEHKTDLNPD | ||||||
Sequence conflict | 98-99 | in Ref. 1; AAA76851 | ||||
Sequence: GG → RR | ||||||
Sequence conflict | 105-106 | in Ref. 1; AAA76851 | ||||
Sequence: EH → DD | ||||||
Sequence conflict | 130 | in Ref. 3; AAA76850 | ||||
Sequence: R → G | ||||||
Sequence conflict | 132 | in Ref. 1; AAA76851 | ||||
Sequence: R → A | ||||||
Sequence conflict | 144 | in Ref. 6; CAG47064 | ||||
Sequence: P → Q | ||||||
Sequence conflict | 203 | in Ref. 2; AAC31758 | ||||
Sequence: L → S | ||||||
Sequence conflict | 215-216 | in Ref. 1; AAA76851 | ||||
Sequence: RG → AR | ||||||
Sequence conflict | 296 | in Ref. 1; AAA76851 | ||||
Sequence: H → D | ||||||
Sequence conflict | 358 | in Ref. 5; BAG35211 | ||||
Sequence: K → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M16451 EMBL· GenBank· DDBJ | AAA76851.1 EMBL· GenBank· DDBJ | mRNA | ||
M21243 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21237 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21238 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21239 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21240 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21241 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M21242 EMBL· GenBank· DDBJ | AAC31758.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L47647 EMBL· GenBank· DDBJ | AAA76852.1 EMBL· GenBank· DDBJ | mRNA | ||
M16364 EMBL· GenBank· DDBJ | AAA76850.1 EMBL· GenBank· DDBJ | mRNA | ||
X15334 EMBL· GenBank· DDBJ | CAA33389.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK290101 EMBL· GenBank· DDBJ | BAF82790.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312282 EMBL· GenBank· DDBJ | BAG35211.1 EMBL· GenBank· DDBJ | mRNA | ||
CR542268 EMBL· GenBank· DDBJ | CAG47064.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ333313 EMBL· GenBank· DDBJ | ABC67465.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471061 EMBL· GenBank· DDBJ | EAW81822.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001190 EMBL· GenBank· DDBJ | AAH01190.1 EMBL· GenBank· DDBJ | mRNA | ||
BC004914 EMBL· GenBank· DDBJ | AAH04914.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008323 EMBL· GenBank· DDBJ | AAH08323.1 EMBL· GenBank· DDBJ | mRNA | ||
BC010002 EMBL· GenBank· DDBJ | AAH10002.1 EMBL· GenBank· DDBJ | mRNA | ||
BC019259 EMBL· GenBank· DDBJ | AAH19259.1 EMBL· GenBank· DDBJ | mRNA | ||
BC019281 EMBL· GenBank· DDBJ | AAH19281.1 EMBL· GenBank· DDBJ | mRNA | ||
M22356 EMBL· GenBank· DDBJ | AAA52024.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M22355 EMBL· GenBank· DDBJ | AAA52024.1 EMBL· GenBank· DDBJ | Genomic DNA |