P12277 (KCRB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Creatine kinase B-type
EC=2.7.3.2

Alternative name(s):
B-CK
Creatine kinase B chain

Gene names

Name:	CKB
Synonyms:	CKBB

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	381 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). 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.
Catalytic activity	ATP + creatine = ADP + phosphocreatine.
Subunit structure	Dimer of identical or non-identical chains. With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the ATP:guanido phosphotransferase family. Contains 1 phosphagen kinase C-terminal domain. Contains 1 phosphagen kinase N-terminal domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from electronic annotation. Source: Compara cellular chloride ion homeostasis Inferred from electronic annotation. Source: Compara cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome creatine metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW creatine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASB9	Q96DX5	3	EBI-357706,EBI-745641

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.11 Ref.12

Chain

2 – 381

380

Creatine kinase B-type

PRO_0000211966

Regions

Domain

11 – 98

88

Phosphagen kinase N-terminal

Domain

125 – 367

243

Phosphagen kinase C-terminal

Nucleotide binding

128 – 132

5

ATP

Nucleotide binding

320 – 325

6

ATP

Sites

Binding site

72

1

Substrate; via amide nitrogen

Binding site

130

1

ATP

Binding site

132

1

ATP

Binding site

191

1

ATP

Binding site

232

1

Substrate

Binding site

236

1

ATP

Binding site

285

1

Substrate

Binding site

292

1

ATP

Binding site

320

1

ATP

Binding site

335

1

ATP By similarity

Amino acid modifications

Modified residue

4

1

Phosphoserine Ref.16

Modified residue

35

1

Phosphothreonine Ref.15

Modified residue

39

1

Phosphotyrosine By similarity

Modified residue

125

1

Phosphotyrosine By similarity

Modified residue

164

1

Phosphoserine By similarity

Modified residue

199

1

Phosphoserine Ref.15

Natural variations

Natural variant

177

1

K → R. Ref.7
Corresponds to variant rs36002620 [ dbSNP | Ensembl ].

VAR_025838

Natural variant

309

1

S → L. Ref.7
Corresponds to variant rs35156510 [ dbSNP | Ensembl ].

VAR_025839

Natural variant

360

1

L → F.
Corresponds to variant rs12505 [ dbSNP | Ensembl ].

VAR_049674

Experimental info

Mutagenesis

283

1

C → S or Y: Complete loss of activity. Ref.14

Mutagenesis

292

1

R → H, L or Q: Complete loss of activity. Ref.14

Mutagenesis

292

1

R → K: 42% of wild-type activity. Ref.14

Mutagenesis

340

1

D → E: No change in activity. Ref.14

Sequence conflict

41 – 42

2

EL → DV in AAA76851. Ref.1

Sequence conflict

78

1

D → G in AAA76850. Ref.3

Sequence conflict

78

1

D → G in AAA52024. Ref.10

Sequence conflict

98 – 99

2

GG → RR in AAA76851. Ref.1

Sequence conflict

105 – 106

2

EH → DD in AAA76851. Ref.1

Sequence conflict

130

1

R → G in AAA76850. Ref.3

Sequence conflict

132

1

R → A in AAA76851. Ref.1

Sequence conflict

144

1

P → Q in CAG47064. Ref.6

Sequence conflict

203

1

L → S in AAC31758. Ref.2

Sequence conflict

215 – 216

2

RG → AR in AAA76851. Ref.1

Sequence conflict

296

1

H → D in AAA76851. Ref.1

Sequence conflict

358

1

K → R in BAG35211. Ref.5

Secondary structure

1

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381

Helix Strand Turn

Details...

Helix

7 – 11

5

Helix

16 – 19

4

Helix

29 – 33

5

Helix

36 – 42

7

Helix

53 – 62

10

Beta strand

67 – 69

3

Helix

81 – 84

4

Helix

86 – 96

11

Helix

112 – 114

3

Turn

123 – 125

3

Beta strand

126 – 135

10

Turn

143 – 145

3

Helix

148 – 162

15

Helix

167 – 169

3

Beta strand

171 – 176

6

Helix

181 – 189

9

Helix

200 – 203

4

Turn

204 – 214

11

Beta strand

216 – 220

5

Beta strand

223 – 244

22

Helix

246 – 266

21

Turn

275 – 277

3

Helix

284 – 286

3

Beta strand

292 – 298

7

Helix

300 – 303

4

Helix

308 – 314

7

Beta strand

317 – 321

5

Helix

325 – 330

6

Beta strand

333 – 338

6

Beta strand

342 – 344

3

Helix

346 – 368

23

Helix

374 – 376

3

Sequences

	Sequence		Length	Mass (Da)
	P12277 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 637AA67A86AE3059	FASTA	381	42,644
	10 20 30 40 50 60 MPFSNSHNAL KLRFPAEDEF PDLSAHNNHM AKVLTPELYA ELRAKSTPSG FTLDDVIQTG 70 80 90 100 110 120 VDNPGHPYIM TVGCVAGDEE SYEVFKDLFD PIIEDRHGGY KPSDEHKTDL NPDNLQGGDD 130 140 150 160 170 180 LDPNYVLSSR VRTGRSIRGF CLPPHCSRGE RRAIEKLAVE ALSSLDGDLA GRYYALKSMT 190 200 210 220 230 240 EAEQQQLIDD HFLFDKPVSP LLLASGMARD WPDARGIWHN DNKTFLVWVN EEDHLRVISM 250 260 270 280 290 300 QKGGNMKEVF TRFCTGLTQI ETLFKSKDYE FMWNPHLGYI LTCPSNLGTG LRAGVHIKLP 310 320 330 340 350 360 NLGKHEKFSE VLKRLRLQKR GTGGVDTAAV GGVFDVSNAD RLGFSEVELV QMVVDGVKLL 370 380 IEMEQRLEQG QAIDDLMPAQ K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human creatine kinase: isolation and sequence analysis of cDNA clones for the B subunit, development of subunit specific probes and determination of gene copy number." Villarreal-Levy G., Ma T.S., Kerner S.A., Roberts R., Perryman M.B. Biochem. Biophys. Res. Commun. 144:1116-1127(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and expression of the human creatine kinase B gene." Mariman E.C.M., Broers C.A.M., Claesen C.A.A., Tesser G.I., Wieringa B. Genomics 1:126-137(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Human creatine kinase-B complementary DNA. Nucleotide sequence, gene expression in lung cancer, and chromosomal assignment to two distinct loci." Kaye F.J., McBride O.W., Battey J.F., Gazder A.F., Sausville E.A. J. Clin. Invest. 79:1412-1420(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Complete nucleotide sequence of the human creatine kinase B gene." Mariman E.C.M., Schepens J.T.G., Wieringa B. Nucleic Acids Res. 17:6385-6385(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Brain.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum and Subthalamic nucleus.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	NIEHS SNPs program Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-177 AND LEU-309.
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Eye and Lung.
[10]	"Isolation of a functional human gene for brain creatine kinase." Daouk G.H., Kaddurah-Daouk R., Putney S., Kingston R., Schimmel P. J. Biol. Chem. 263:2442-2446(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-97.
[11]	"Protein analysis of human maculae in relation to age-related maculopathy." Kliffen M., de Jong P.T.V.M., Luider T.M. Lab. Invest. 73:267-272(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-22. Tissue: Eye.
[12]	Bienvenut W.V., Heiserich L., Gottlieb E. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11; 33-43; 157-172; 224-236; 253-265; 308-314 AND 342-366, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[13]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 33-43; 87-96; 108-130; 157-172; 224-236; 253-265; 320-341 AND 359-381, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[14]	"Determination of the catalytic site of creatine kinase by site-directed mutagenesis." Lin L., Perryman M.B., Friedman D., Roberts R., Ma T.S. Biochim. Biophys. Acta 1206:97-104(1994) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-283; ARG-292 AND ASP-340.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-35 AND SER-199, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"Structural studies of human brain-type creatine kinase complexed with the ADP-Mg2+-NO3- -creatine transition-state analogue complex." Bong S.M., Moon J.H., Nam K.H., Lee K.S., Chi Y.M., Hwang K.Y. FEBS Lett. 582:3959-3965(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH ADP AND CREATINE, ATP-BINDING SITES, SUBSTRATE-BINDING SITES.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Creatine kinase entry

Wikipedia

CKB entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16451 mRNA. Translation: AAA76851.1.
M21243 , M21237, M21238, M21239, M21240, M21241, M21242 Genomic DNA. Translation: AAC31758.1.
L47647 mRNA. Translation: AAA76852.1.
M16364 mRNA. Translation: AAA76850.1.
X15334 Genomic DNA. Translation: CAA33389.1.
AK290101 mRNA. Translation: BAF82790.1.
AK312282 mRNA. Translation: BAG35211.1.
CR542268 mRNA. Translation: CAG47064.1.
DQ333313 Genomic DNA. Translation: ABC67465.1.
CH471061 Genomic DNA. Translation: EAW81822.1.
BC001190 mRNA. Translation: AAH01190.1.
BC004914 mRNA. Translation: AAH04914.1.
BC008323 mRNA. Translation: AAH08323.1.
BC010002 mRNA. Translation: AAH10002.1.
BC019259 mRNA. Translation: AAH19259.1.
BC019281 mRNA. Translation: AAH19281.1.
M22356, M22355 Genomic DNA. Translation: AAA52024.1.

IPI

IPI00022977.

PIR

KIHUCB. S15935.

RefSeq

NP_001814.2. NM_001823.4.

UniGene

Hs.173724.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3B6R	X-ray	2.00	A/B	1-381	[»]
3DRB	X-ray	2.00	A/B	1-381	[»]
3DRE	X-ray	2.20	A/B	1-381	[»]

ProteinModelPortal

P12277.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12277. 19 interactions.

MINT

MINT-1484821.

STRING

9606.ENSP00000299198.

PTM databases

PhosphoSite

P12277.

Polymorphism databases

DMDM

125294.

2D gel databases

REPRODUCTION-2DPAGE

IPI00022977.
P12277.

UCD-2DPAGE

P12277.

Proteomic databases

PaxDb

P12277.

PeptideAtlas

P12277.

PRIDE

P12277.

Protocols and materials databases

DNASU

1152.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000348956; ENSP00000299198; ENSG00000166165.

GeneID

1152.

KEGG

hsa:1152.

UCSC

uc001ynf.2. human.

Organism-specific databases

CTD

1152.

GeneCards

GC14M103986.

HGNC

HGNC:1991. CKB.

HPA

CAB047313.
HPA001254.

MIM

123280. gene.

neXtProt

NX_P12277.

PharmGKB

PA26528.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3869.

HOGENOM

HOG000232165.

HOVERGEN

HBG001339.

InParanoid

P12277.

KO

K00933.

OMA

RGHEFMW.

OrthoDB

EOG4R7V9X.

PhylomeDB

P12277.

Enzyme and pathway databases

BioCyc

MetaCyc:HS09344-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P12277.

Gene expression databases

ArrayExpress

P12277.

Bgee

P12277.

CleanEx

HS_CKB.

Genevestigator

P12277.

Family and domain databases

Gene3D

1.10.135.10. 1 hit.
3.30.590.10. 1 hit.

InterPro

IPR000749. ATP-guanido_PTrfase.
IPR022415. ATP-guanido_PTrfase_AS.
IPR022414. ATP-guanido_PTrfase_cat.
IPR022413. ATP-guanido_PTrfase_N.
IPR014746. Gln_synth/guanido_kin_cat_dom.
[Graphical view]

PANTHER

PTHR11547. PTHR11547. 1 hit.

Pfam

PF00217. ATP-gua_Ptrans. 1 hit.
PF02807. ATP-gua_PtransN. 1 hit.
[Graphical view]

SUPFAM

SSF48034. ATP-gua_Ptrans. 1 hit.

PROSITE

PS00112. PHOSPHAGEN_KINASE. 1 hit.
PS51510. PHOSPHAGEN_KINASE_C. 1 hit.
PS51509. PHOSPHAGEN_KINASE_N. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL6049.

ChiTaRS

CKB. human.

DrugBank

DB00148. Creatine.

EvolutionaryTrace

P12277.

GenomeRNAi

1152.

NextBio

4784.

SOURCE

Search...

Entry information

Entry name

KCRB_HUMAN

Accession

Primary (citable) accession number: P12277
Secondary accession number(s): A8K236 , B2R5R4, Q2LE07, Q6FG40, Q9UC66

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 143 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.