KCRS_HUMAN
ID KCRS_HUMAN Reviewed; 419 AA.
AC P17540; Q6ICS8; Q8N1E1;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Creatine kinase S-type, mitochondrial;
DE EC=2.7.3.2;
DE AltName: Full=Basic-type mitochondrial creatine kinase;
DE Short=Mib-CK;
DE AltName: Full=Sarcomeric mitochondrial creatine kinase;
DE Short=S-MtCK;
DE Flags: Precursor;
GN Name=CKMT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=2324105; DOI=10.1016/s0021-9258(19)39237-3;
RA Haas R.C., Strauss A.W.;
RT "Separate nuclear genes encode sarcomere-specific and ubiquitous human
RT mitochondrial creatine kinase isoenzymes.";
RL J. Biol. Chem. 265:6921-6927(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 40-65.
RX PubMed=2914937; DOI=10.1016/s0021-9258(19)81696-4;
RA Haas R.C., Korenfeld C., Zhang Z., Perryman B., Roman D., Strauss A.W.;
RT "Isolation and characterization of the gene and cDNA encoding human
RT mitochondrial creatine kinase.";
RL J. Biol. Chem. 264:2890-2897(1989).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 27-416 IN COMPLEX WITH ADP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human sarcomeric mitochondrial creatine kinase.";
RL Submitted (APR-2006) to the PDB data bank.
CC -!- FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP
CC and various phosphogens (e.g. creatine phosphate). Creatine kinase
CC isoenzymes play a central role in energy transduction in tissues with
CC large, fluctuating energy demands, such as skeletal muscle, heart,
CC brain and spermatozoa.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + creatine = ADP + H(+) + N-phosphocreatine;
CC Xref=Rhea:RHEA:17157, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57947, ChEBI:CHEBI:58092, ChEBI:CHEBI:456216; EC=2.7.3.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10029};
CC -!- SUBUNIT: Exists as an octamer composed of four CKMT2 homodimers.
CC {ECO:0000269|Ref.5}.
CC -!- INTERACTION:
CC P17540; O15182: CETN3; NbExp=3; IntAct=EBI-712973, EBI-712959;
CC P17540; Q9P2K6: KLHL42; NbExp=3; IntAct=EBI-712973, EBI-739890;
CC P17540; Q16656-4: NRF1; NbExp=3; IntAct=EBI-712973, EBI-11742836;
CC P17540; Q7Z4N8: P4HA3; NbExp=3; IntAct=EBI-712973, EBI-10181968;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane
CC protein; Intermembrane side.
CC -!- TISSUE SPECIFICITY: Sarcomere-specific. Found only in heart and
CC skeletal muscles.
CC -!- MISCELLANEOUS: Mitochondrial creatine kinase binds cardiolipin.
CC -!- SIMILARITY: Belongs to the ATP:guanido phosphotransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU00842, ECO:0000255|PROSITE-
CC ProRule:PRU00843}.
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DR EMBL; J05401; AAA60561.1; -; mRNA.
DR EMBL; CR450315; CAG29311.1; -; mRNA.
DR EMBL; BC029140; AAH29140.1; -; mRNA.
DR CCDS; CCDS4053.1; -.
DR PIR; A35756; A35756.
DR RefSeq; NP_001093205.1; NM_001099735.1.
DR RefSeq; NP_001093206.1; NM_001099736.1.
DR RefSeq; NP_001816.2; NM_001825.2.
DR PDB; 4Z9M; X-ray; 2.10 A; A/B/C/D/E/F/G/H=27-416.
DR PDBsum; 4Z9M; -.
DR AlphaFoldDB; P17540; -.
DR SMR; P17540; -.
DR BioGRID; 107580; 33.
DR IntAct; P17540; 15.
DR STRING; 9606.ENSP00000404203; -.
DR DrugBank; DB00787; Acyclovir.
DR DrugBank; DB00148; Creatine.
DR DrugBank; DB13191; Phosphocreatine.
DR DrugBank; DB00300; Tenofovir disoproxil.
DR GlyGen; P17540; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P17540; -.
DR PhosphoSitePlus; P17540; -.
DR BioMuta; CKMT2; -.
DR DMDM; 116242603; -.
DR UCD-2DPAGE; P17540; -.
DR EPD; P17540; -.
DR jPOST; P17540; -.
DR MassIVE; P17540; -.
DR MaxQB; P17540; -.
DR PaxDb; P17540; -.
DR PeptideAtlas; P17540; -.
DR PRIDE; P17540; -.
DR ProteomicsDB; 53483; -.
DR Antibodypedia; 12782; 427 antibodies from 34 providers.
DR DNASU; 1160; -.
DR Ensembl; ENST00000254035.9; ENSP00000254035.4; ENSG00000131730.16.
DR Ensembl; ENST00000424301.6; ENSP00000404203.2; ENSG00000131730.16.
DR Ensembl; ENST00000437669.5; ENSP00000410289.1; ENSG00000131730.16.
DR GeneID; 1160; -.
DR KEGG; hsa:1160; -.
DR MANE-Select; ENST00000254035.9; ENSP00000254035.4; NM_001099735.2; NP_001093205.1.
DR UCSC; uc003khc.5; human.
DR CTD; 1160; -.
DR DisGeNET; 1160; -.
DR GeneCards; CKMT2; -.
DR HGNC; HGNC:1996; CKMT2.
DR HPA; ENSG00000131730; Group enriched (heart muscle, skeletal muscle, tongue).
DR MIM; 123295; gene.
DR neXtProt; NX_P17540; -.
DR OpenTargets; ENSG00000131730; -.
DR PharmGKB; PA26534; -.
DR VEuPathDB; HostDB:ENSG00000131730; -.
DR eggNOG; KOG3581; Eukaryota.
DR GeneTree; ENSGT00950000182772; -.
DR HOGENOM; CLU_019868_4_2_1; -.
DR InParanoid; P17540; -.
DR OMA; ECLTPTI; -.
DR OrthoDB; 825025at2759; -.
DR PhylomeDB; P17540; -.
DR TreeFam; TF314214; -.
DR BioCyc; MetaCyc:HS05555-MON; -.
DR PathwayCommons; P17540; -.
DR Reactome; R-HSA-71288; Creatine metabolism.
DR SignaLink; P17540; -.
DR SIGNOR; P17540; -.
DR BioGRID-ORCS; 1160; 8 hits in 1066 CRISPR screens.
DR EvolutionaryTrace; P17540; -.
DR GeneWiki; CKMT2; -.
DR GenomeRNAi; 1160; -.
DR Pharos; P17540; Tbio.
DR PRO; PR:P17540; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P17540; protein.
DR Bgee; ENSG00000131730; Expressed in heart right ventricle and 153 other tissues.
DR ExpressionAtlas; P17540; baseline and differential.
DR Genevisible; P17540; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004111; F:creatine kinase activity; IBA:GO_Central.
DR GO; GO:0016301; F:kinase activity; IBA:GO_Central.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0046314; P:phosphocreatine biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.135.10; -; 1.
DR InterPro; IPR000749; ATP-guanido_PTrfase.
DR InterPro; IPR022415; ATP-guanido_PTrfase_AS.
DR InterPro; IPR022414; ATP-guanido_PTrfase_cat.
DR InterPro; IPR022413; ATP-guanido_PTrfase_N.
DR InterPro; IPR036802; ATP-guanido_PTrfase_N_sf.
DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR PANTHER; PTHR11547; PTHR11547; 1.
DR Pfam; PF00217; ATP-gua_Ptrans; 1.
DR Pfam; PF02807; ATP-gua_PtransN; 1.
DR SUPFAM; SSF48034; SSF48034; 1.
DR SUPFAM; SSF55931; SSF55931; 1.
DR PROSITE; PS00112; PHOSPHAGEN_KINASE; 1.
DR PROSITE; PS51510; PHOSPHAGEN_KINASE_C; 1.
DR PROSITE; PS51509; PHOSPHAGEN_KINASE_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing; Kinase; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2914937"
FT CHAIN 40..419
FT /note="Creatine kinase S-type, mitochondrial"
FT /id="PRO_0000016594"
FT DOMAIN 46..132
FT /note="Phosphagen kinase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00842"
FT DOMAIN 159..401
FT /note="Phosphagen kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00843"
FT REGION 40..64
FT /note="Cardiolipin-binding"
FT /evidence="ECO:0000250"
FT BINDING 162..166
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 225
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00843"
FT BINDING 326
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 354..359
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 369
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 255
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P09605"
FT MOD_RES 356
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6P8J7"
FT CONFLICT 74
FT /note="A -> S (in Ref. 1; AAA60561)"
FT /evidence="ECO:0000305"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 63..67
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 70..76
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 87..96
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 120..130
FT /evidence="ECO:0007829|PDB:4Z9M"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:4Z9M"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:4Z9M"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 160..169
FT /evidence="ECO:0007829|PDB:4Z9M"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 182..196
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 215..223
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 234..237
FT /evidence="ECO:0007829|PDB:4Z9M"
FT TURN 238..248
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 257..278
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 280..300
FT /evidence="ECO:0007829|PDB:4Z9M"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 326..332
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 334..338
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 342..348
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 367..373
FT /evidence="ECO:0007829|PDB:4Z9M"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 380..396
FT /evidence="ECO:0007829|PDB:4Z9M"
FT HELIX 398..402
FT /evidence="ECO:0007829|PDB:4Z9M"
SQ SEQUENCE 419 AA; 47504 MW; 0CAF000074D99B6F CRC64;
MASIFSKLLT GRNASLLFAT MGTSVLTTGY LLNRQKVCAE VREQPRLFPP SADYPDLRKH
NNCMAECLTP AIYAKLRNKV TPNGYTLDQC IQTGVDNPGH PFIKTVGMVA GDEESYEVFA
DLFDPVIKLR HNGYDPRVMK HTTDLDASKI TQGQFDEHYV LSSRVRTGRS IRGLSLPPAC
TRAERREVEN VAITALEGLK GDLAGRYYKL SEMTEQDQQR LIDDHFLFDK PVSPLLTCAG
MARDWPDARG IWHNYDKTFL IWINEEDHTR VISMEKGGNM KRVFERFCRG LKEVERLIQE
RGWEFMWNER LGYILTCPSN LGTGLRAGVH VRIPKLSKDP RFSKILENLR LQKRGTGGVD
TAAVADVYDI SNIDRIGRSE VELVQIVIDG VNYLVDCEKK LERGQDIKVP PPLPQFGKK
