Q14896 (MYPC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myosin-binding protein C, cardiac-type
Short name=Cardiac MyBP-C

Alternative name(s):
C-protein, cardiac muscle isoform

Gene names

Name:

MYBPC3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1273 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.
Post-translational modification	Substrate for phosphorylation by PKA and PKC. Reversible phosphorylation appears to modulate contraction By similarity.
Involvement in disease	Defects in MYBPC3 are the cause of familial hypertrophic cardiomyopathy type 4 (CMH4) [MIM:115197]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Ref.1 Ref.2 Ref.3 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30
Sequence similarities	Belongs to the immunoglobulin superfamily. MyBP family. Contains 3 fibronectin type-III domains. Contains 7 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Thick filament
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Immunoglobulin domain Repeat
Ligand	Actin-binding Metal-binding Zinc
Molecular function	Muscle protein
PTM	Acetylation Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cardiac muscle contraction Inferred from sequence or structural similarity. Source: BHF-UCL cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW muscle filament sliding Traceable author statement. Source: Reactome regulation of muscle filament sliding Inferred from sequence or structural similarity. Source: BHF-UCL regulation of striated muscle contraction Inferred from sequence or structural similarity. Source: BHF-UCL ventricular cardiac muscle tissue morphogenesis Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	C zone Non-traceable author statement. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome striated muscle myosin thick filament Inferred from direct assay. Source: BHF-UCL
Molecular function	ATPase activator activity Inferred from sequence or structural similarity. Source: BHF-UCL actin binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW myosin heavy chain binding Inferred from physical interaction. Source: BHF-UCL structural constituent of muscle Inferred from mutant phenotype. Source: BHF-UCL titin binding Non-traceable author statement. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1273

1273

Myosin-binding protein C, cardiac-type

PRO_0000072693

Regions

Domain

153 – 256

104

Ig-like C2-type 1

Domain

362 – 451

90

Ig-like C2-type 2

Domain

452 – 542

91

Ig-like C2-type 3

Domain

543 – 632

90

Ig-like C2-type 4

Domain

644 – 770

127

Ig-like C2-type 5

Domain

771 – 863

93

Fibronectin type-III 1

Domain

868 – 961

94

Fibronectin type-III 2

Domain

970 – 1064

95

Ig-like C2-type 6

Domain

1065 – 1157

93

Fibronectin type-III 3

Domain

1180 – 1273

94

Ig-like C2-type 7

Compositional bias

102 – 152

51

Pro-rich

Sites

Metal binding

208

1

Zinc

Metal binding

210

1

Zinc

Metal binding

223

1

Zinc

Metal binding

225

1

Zinc

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

275

1

Phosphoserine; by PKA and PKC By similarity

Modified residue

284

1

Phosphoserine; by PKA and PKC By similarity

Modified residue

304

1

Phosphoserine; by PKA and PKC By similarity

Disulfide bond

435 ↔ 442

Potential

Natural variations

Natural variant

5

1

G → R in CMH4. Ref.26

VAR_029390

Natural variant

59

1

T → A in CMH4. Ref.17

VAR_029391

Natural variant

158

1

V → M. Ref.4 Ref.26 Ref.30
Corresponds to variant rs3729986 [ dbSNP | Ensembl ].

VAR_020085

Natural variant

161

1

P → S in CMH4. Ref.22

VAR_029392

Natural variant

189

1

V → I. Ref.4
Corresponds to variant rs11570052 [ dbSNP | Ensembl ].

VAR_020568

Natural variant

219

1

V → L in CMH4. Ref.26

VAR_029393

Natural variant

228

1

D → N in CMH4. Ref.25

VAR_029394

Natural variant

236

1

S → G. Ref.4 Ref.16 Ref.21 Ref.26 Ref.27 Ref.30
Corresponds to variant rs3729989 [ dbSNP | Ensembl ].

VAR_020086

Natural variant

237

1

Y → S in CMH4. Ref.24

VAR_029395

Natural variant

256

1

V → I in CMH4. Ref.26

VAR_029396

Natural variant

257

1

H → P in CMH4. Ref.19

VAR_019889

Natural variant

258

1

E → K in CMH4. Ref.18 Ref.19 Ref.21 Ref.22 Ref.25 Ref.26 Ref.28

VAR_019890

Natural variant

263

1

G → R in CMH4. Ref.28

VAR_042740

Natural variant

273

1

R → H in CMH4. Ref.29

VAR_042741

Natural variant

278

1

G → E in CMH4. Ref.19 Ref.30

VAR_019891

Natural variant

279

1

G → A in CMH4. Ref.19

VAR_019892

Natural variant

281

1

R → Q. Ref.4
Corresponds to variant rs11570060 [ dbSNP | Ensembl ].

VAR_020569

Natural variant

282

1

R → W in CMH4. Ref.15 Ref.21

VAR_029397

Natural variant

326

1

R → Q. Ref.14 Ref.16 Ref.17 Ref.19 Ref.21 Ref.24 Ref.26 Ref.29 Ref.30
Corresponds to variant rs34580776 [ dbSNP | Ensembl ].

VAR_019893

Natural variant

352

1

L → P in CMH4. Ref.19

VAR_019894

Natural variant

382

1

R → W. Ref.4 Ref.26
Corresponds to variant rs11570076 [ dbSNP | Ensembl ].

VAR_020570

Natural variant

383

1

L → V. Ref.4
Corresponds to variant rs11570077 [ dbSNP | Ensembl ].

VAR_020571

Natural variant

415

1

G → S. Ref.26

VAR_029398

Natural variant

416

1

A → S in CMH4. Ref.28

VAR_042742

Natural variant

450

1

E → Q in CMH4. Ref.3

VAR_027879

Natural variant

457

1

R → H in CMH4. Ref.26

VAR_029399

Natural variant

489

1

G → R in CMH4. Ref.26 Ref.30

VAR_029400

Natural variant

494

1

R → G in CMH4. Ref.30

VAR_045929

Natural variant

494

1

R → Q in CMH4. Ref.3 Ref.14 Ref.26

VAR_027880

Natural variant

501

1

R → Q in CMH4. Ref.3 Ref.30

VAR_027881

Natural variant

501

1

R → W in CMH4. Ref.19 Ref.26 Ref.29 Ref.30

VAR_019895

Natural variant

503

1

Missing in CMH4.

VAR_019896

Natural variant

506

1

G → R in CMH4. Ref.15 Ref.21 Ref.26
Corresponds to variant rs35736435 [ dbSNP | Ensembl ].

VAR_029401

Natural variant

521

1

A → T. Ref.4
Corresponds to variant rs11570082 [ dbSNP | Ensembl ].

VAR_020573

Natural variant

522

1

G → W in CMH4. Ref.21

VAR_029402

Natural variant

541

1

E → Q in CMH4. Ref.2 Ref.19 Ref.26 Ref.29

VAR_003917

Natural variant

544

1

L → M. Ref.26

VAR_029403

Natural variant

565

1

C → R in CMH4. Ref.15 Ref.21

VAR_029404

Natural variant

603

1

D → V in CMH4. Ref.26

VAR_029405

Natural variant

604

1

D → N in CMH4; pathogenicity remains to be determined. Ref.22 Ref.26 Ref.30

VAR_029406

Natural variant

607

1

P → L in CMH4. Ref.26

VAR_029407

Natural variant

653

1

R → H in CMH4; as well folded and stable as the wild-type. Ref.6 Ref.12
Corresponds to variant rs1800565 [ dbSNP | Ensembl ].

VAR_003918

Natural variant

667

1

R → H in CMH4. Ref.24

VAR_029408

Natural variant

667

1

R → P in CMH4. Ref.21

VAR_029409

Natural variant

668

1

L → H in CMH4. Ref.28

VAR_042743

Natural variant

732

1

R → C in CMH4. Ref.26

VAR_029410

Natural variant

754

1

N → K in CMH4; destabilizes the structure of Ig-like C2-type domain 5. Ref.6 Ref.11

VAR_003919

Natural variant

758

1

E → D in CMH4. Ref.28

VAR_042744

Natural variant

769

1

D → N in CMH4. Ref.26
Corresponds to variant rs36211723 [ dbSNP | Ensembl ].

VAR_029411

Natural variant

791

1

W → R in CMH4. Ref.26

VAR_029412

Natural variant

809

1

R → H in CMH4. Ref.18 Ref.26

VAR_029413

Natural variant

810

1

K → R in CMH4. Ref.19

VAR_019897

Natural variant

810

1

Missing in CMH4.

VAR_029414

Natural variant

812

1

Missing in CMH4.

VAR_029415

Natural variant

819

1

R → Q in CMH4. Ref.1 Ref.2 Ref.18 Ref.23
Corresponds to variant rs2856655 [ dbSNP | Ensembl ].

VAR_029416

Natural variant

832

1

A → T in CMH4; pathogenicity is uncertain. Ref.22 Ref.24 Ref.25 Ref.26

VAR_029417

Natural variant

832

1

A → V in CMH4. Ref.4 Ref.19 Ref.21
Corresponds to variant rs3729952 [ dbSNP | Ensembl ].

VAR_019898

Natural variant

833

1

R → T in CMH4.

VAR_029418

Natural variant

833

1

R → W in CMH4; pathogenicity is uncertain. Ref.22

VAR_029419

Natural variant

872

1

P → H in CMH4. Ref.18

VAR_029420

Natural variant

895

1

V → M May act as a phenotype modifier in cardiomyopathy patients. Ref.13 Ref.19 Ref.24 Ref.26 Ref.30
Corresponds to variant rs35078470 [ dbSNP | Ensembl ].

VAR_019899

Natural variant

947

1

N → T in CMH4. Ref.16

VAR_029421

Natural variant

997

1

Q → E in CMH4; dbNP:11570112. Ref.4 Ref.26

VAR_020574

Natural variant

997

1

Q → R in CMH4. Ref.26

VAR_029422

Natural variant

1001

1

R → Q in CMH4. Ref.17

VAR_029423

Natural variant

1001

1

R → W. Ref.30
Corresponds to variant rs3729799 [ dbSNP | Ensembl ].

VAR_029424

Natural variant

1002

1

P → Q in CMH4.

VAR_029425

Natural variant

1027

1

T → S in CMH4. Ref.30

VAR_045930

Natural variant

1047

1

R → C. Ref.4
Corresponds to variant rs11570113 [ dbSNP | Ensembl ].

VAR_020575

Natural variant

1112

1

F → I in CMH4. Ref.26

VAR_029426

Natural variant

1114

1

V → I in CMH4. Ref.15 Ref.21

VAR_029427

Natural variant

1130

1

I → T in CMH4; pathogenicity is uncertain. Ref.22 Ref.26

VAR_029428

Natural variant

1154

1

Missing in CMH4.

VAR_029429

Natural variant

1193

1

A → T in CMH4. Ref.19

VAR_019900

Natural variant

1247

1

G → R in CMH4. Ref.30

VAR_045931

Natural variant

1254

1

A → T in CMH4. Ref.19

VAR_019901

Experimental info

Sequence conflict

248

1

D → E Ref.1

Sequence conflict

248

1

D → E Ref.2

Sequence conflict

302 – 303

2

SS → RD in CAA58882. Ref.1

Sequence conflict

302 – 303

2

SS → RD in CAA71216. Ref.2

Sequence conflict

302 – 303

2

SS → RD in AAC04620. Ref.3

Sequence conflict

408

1

R → SK in CAA58882. Ref.1

Sequence conflict

408

1

R → SK in CAA71216. Ref.2

Sequence conflict

408

1

R → SK in AAC04620. Ref.3

Sequence conflict

535

1

A → R in CAA58882. Ref.1

Secondary structure

1

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1273

Helix Strand Turn

Details...

Beta strand

164 – 167

4

Beta strand

172 – 179

8

Beta strand

188 – 193

6

Turn

194 – 196

3

Helix

199 – 202

4

Beta strand

207 – 214

8

Turn

215 – 218

4

Beta strand

219 – 226

8

Helix

231 – 233

3

Beta strand

235 – 242

8

Beta strand

247 – 257

11

Beta strand

649 – 651

3

Beta strand

657 – 664

8

Beta strand

669 – 671

3

Beta strand

674 – 676

3

Beta strand

679 – 685

7

Beta strand

721 – 723

3

Beta strand

725 – 729

5

Beta strand

732 – 736

5

Turn

742 – 744

3

Beta strand

746 – 753

8

Beta strand

758 – 767

10

Sequences

	Sequence		Length	Mass (Da)
	Q14896 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 77744F1FC63F5F7A	FASTA	1,273	140,606
	10 20 30 40 50 60 MPEPGKKPVS AFSKKPRSVE VAAGSPAVFE AETERAGVKV RWQRGGSDIS ASNKYGLATE 70 80 90 100 110 120 GTRHTLTVRE VGPADQGSYA VIAGSSKVKF DLKVIEAEKA EPMLAPAPAP AEATGAPGEA 130 140 150 160 170 180 PAPAAELGES APSPKGSSSA ALNGPTPGAP DDPIGLFVMR PQDGEVTVGG SITFSARVAG 190 200 210 220 230 240 ASLLKPPVVK WFKGKWVDLS SKVGQHLQLH DSYDRASKVY LFELHITDAQ PAFTGSYRCE 250 260 270 280 290 300 VSTKDKFDCS NFNLTVHEAM GTGDLDLLSA FRRTSLAGGG RRISDSHEDT GILDFSSLLK 310 320 330 340 350 360 KSSSFRTPRD SKLEAPAEED VWEILRQAPP SEYERIAFQY GVTDLRGMLK RLKGMRRDEK 370 380 390 400 410 420 KSTAFQKKLE PAYQVSKGHK IRLTVELADH DAEVKWLKNG QEIQMSGRYI FESIGAKRTL 430 440 450 460 470 480 TISQCSLADD AAYQCVVGGE KCSTELFVKE PPVLITRPLE DQLVMVGQRV EFECEVSEEG 490 500 510 520 530 540 AQVKWLKDGV ELTREETFKY RFKKDGQRHH LIINEAMLED AGHYALCTSG GQALAELIVQ 550 560 570 580 590 600 EKKLEVYQSI ADLMVGAKDQ AVFKCEVSDE NVRGVWLKNG KELVPDSRIK VSHIGRVHKL 610 620 630 640 650 660 TIDDVTPADE ADYSFVPEGF ACNLSAKLHF MEVKIDFVPR QEPPKIHLDC PGRIPDTIVV 670 680 690 700 710 720 VAGNKLRLDV PISGDPAPTV IWQKAITQGN KAPARPAPDA PEDTGDSDEW VFDKKLLCET 730 740 750 760 770 780 EGRVRVETTK DRSIFTVEGA EKEDEGVYTV TVKNPVGEDQ VNLTVKVIDV PDAPAAPKIS 790 800 810 820 830 840 NVGEDSCTVQ WEPPAYDGGQ PILGYILERK KKKSYRWMRL NFDLIQELSH EARRMIEGVV 850 860 870 880 890 900 YEMRVYAVNA IGMSRPSPAS QPFMPIGPPS EPTHLAVEDV SDTTVSLKWR PPERVGAGGL 910 920 930 940 950 960 DGYSVEYCPE GCSEWVAALQ GLTEHTSILV KDLPTGARLL FRVRAHNMAG PGAPVTTTEP 970 980 990 1000 1010 1020 VTVQEILQRP RLQLPRHLRQ TIQKKVGEPV NLLIPFQGKP RPQVTWTKEG QPLAGEEVSI 1030 1040 1050 1060 1070 1080 RNSPTDTILF IRAARRVHSG TYQVTVRIEN MEDKATLVLQ VVDKPSPPQD LRVTDAWGLN 1090 1100 1110 1120 1130 1140 VALEWKPPQD VGNTELWGYT VQKADKKTME WFTVLEHYRR THCVVPELII GNGYYFRVFS 1150 1160 1170 1180 1190 1200 QNMVGFSDRA ATTKEPVFIP RPGITYEPPN YKALDFSEAP SFTQPLVNRS VIAGYTAMLC 1210 1220 1230 1240 1250 1260 CAVRGSPKPK ISWFKNGLDL GEDARFRMFS KQGVLTLEIR KPCPFDGGIY VCRATNLQGE 1270 ARCECRLEVR VPQ

References

[1]	"Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction?" Gautel M., Zuffardi O., Freiburg A., Labeit S. EMBO J. 14:1952-1960(1995) [PubMed: 7744002] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMH4 GLN-819. Tissue: Heart.
[2]	"Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy." Carrier L., Bonne G., Bahrend E., Yu B., Richard P., Niel F., Hainque B., Cruaud C., Gary F., Labeit S., Bouhour J.-B., Dubourg O., Desnos M., Hagege A.A., Trent R.J., Komajda M., Fiszman M., Schwartz K. Circ. Res. 80:427-434(1997) [PubMed: 9048664] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CMH4 GLN-541 AND GLN-819.
[3]	"Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy." Niimura H., Bachinski L.L., Sangwatanaroj S., Watkins H., Chudley A.E., McKenna W., Kristinsson A., Roberts R., Sole M., Maron B.J., Seidman J.G., Seidman C.E. N. Engl. J. Med. 338:1248-1257(1998) [PubMed: 9562578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CMH4 GLN-450; GLN-494 AND GLN-501.
[4]	NIEHS SNPs program Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-158; ILE-189; GLY-236; GLN-281; TRP-382; VAL-383; THR-521; VAL-832; GLU-997 AND CYS-1047.
[5]	"Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy." Bonne G., Carrier L., Bercovici J., Cruaud C., Richard P., Hainque B., Gautel M., Labeit S., James M., Beckmann J., Weissenbach J., Vosberg H.-P., Fiszman M., Komajda M., Schwartz K. Nat. Genet. 11:438-440(1995) [PubMed: 7493026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 639-693.
[6]	"Structure, stability and dynamics of the central domain of cardiac myosin binding protein C (MyBP-C): implications for multidomain assembly and causes for cardiomyopathy." Idowu S.M., Gautel M., Perkins S.J., Pfuhl M. J. Mol. Biol. 329:745-761(2003) [PubMed: 12787675] [Abstract] Cited for: STRUCTURE BY NMR OF 640-769, CHARACTERIZATION OF VARIANTS HIS-653 AND LYS-754.
[7]	"Sequence specific assignment of domain C1 of the N-terminal myosin-binding site of human cardiac myosin binding protein C (MyBP-C)." Ababou A., Zhou L., Gautel M., Pfuhl M. J. Biomol. NMR 29:431-432(2004) [PubMed: 15213454] [Abstract] Cited for: STRUCTURE BY NMR OF 358-450, POTENTIAL DISULFIDE BOND.
[8]	"An investigation into the protonation states of the C1 domain of cardiac myosin-binding protein C." Fisher S.J., Helliwell J.R., Khurshid S., Govada L., Redwood C., Squire J.M., Chayen N.E. Acta Crystallogr. D 64:658-664(2008) [PubMed: 18560154] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 151-258.
[9]	"Crystal structure of the C1 domain of cardiac myosin binding protein-C: implications for hypertrophic cardiomyopathy." Govada L., Carpenter L., da Fonseca P.C., Helliwell J.R., Rizkallah P., Flashman E., Chayen N.E., Redwood C., Squire J.M. J. Mol. Biol. 378:387-397(2008) [PubMed: 18374358] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 151-258.
[10]	"Myosin binding protein C positioned to play a key role in regulation of muscle contraction: structure and interactions of domain C1." Ababou A., Rostkova E., Mistry S., Le Masurier C., Gautel M., Pfuhl M. J. Mol. Biol. 384:615-630(2008) [PubMed: 18926831] [Abstract] Cited for: STRUCTURE BY NMR OF 151-260, ZINC-BINDING SITE.
[11]	"Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene." Yu B., French J.A., Carrier L., Jeremy R.W., McTaggart D.R., Nicholson M.R., Hambly B., Semsarian C., Richmond D.R., Schwartz K., Trent R.J. J. Med. Genet. 35:205-210(1998) [PubMed: 9541104] [Abstract] Cited for: VARIANT CMH4 LYS-754.
[12]	"Identification of a new missense mutation in MyBP-C associated with hypertrophic cardiomyopathy." Moolman-Smook J.C., Mayosi B., Brink P., Corfield V.A. J. Med. Genet. 35:253-254(1998) [PubMed: 9541115] [Abstract] Cited for: VARIANT CMH4 HIS-653.
[13]	"The origins of hypertrophic cardiomyopathy-causing mutations in two South African subpopulations: a unique profile of both independent and founder events." Moolman-Smook J.C., De Lange W.J., Bruwer E.C.D., Brink P.A., Corfield V.A. Am. J. Hum. Genet. 65:1308-1320(1999) [PubMed: 10521296] [Abstract] Cited for: VARIANT MET-895.
[14]	"Development of left ventricular hypertrophy in adults in hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations." Maron B.J., Niimura H., Casey S.A., Soper M.K., Wright G.B., Seidman J.G., Seidman C.E. J. Am. Coll. Cardiol. 38:315-321(2001) [PubMed: 11499718] [Abstract] Cited for: VARIANT CMH4 GLN-494, VARIANT GLN-326.
[15]	"Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy." Erdmann J., Raible J., Maki-Abadi J., Hummel M., Hammann J., Wollnik B., Frantz E., Fleck E., Hetzer R., Regitz-Zagrosek V. J. Am. Coll. Cardiol. 38:322-330(2001) [PubMed: 11499719] [Abstract] Cited for: VARIANTS CMH4 TRP-282; ARG-506; ARG-565 AND ILE-1114.
[16]	"Novel mutations in sarcomeric protein genes in dilated cardiomyopathy." Daehmlow S., Erdmann J., Knueppel T., Gille C., Froemmel C., Hummel M., Hetzer R., Regitz-Zagrosek V. Biochem. Biophys. Res. Commun. 298:116-120(2002) [PubMed: 12379228] [Abstract] Cited for: VARIANT CMH4 THR-947, VARIANTS GLY-236 AND GLN-326.
[17]	"Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly." Niimura H., Patton K.K., McKenna W.J., Soults J., Maron B.J., Seidman J.G., Seidman C.E. Circulation 105:446-451(2002) [PubMed: 11815426] [Abstract] Cited for: VARIANTS CMH4 ALA-59 AND GLN-1001, VARIANT GLN-326.
[18]	"Hypertrophic cardiomyopathy: two homozygous cases with 'typical' hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy." Nanni L., Pieroni M., Chimenti C., Simionati B., Zimbello R., Maseri A., Frustaci A., Lanfranchi G. Biochem. Biophys. Res. Commun. 309:391-398(2003) [PubMed: 12951062] [Abstract] Cited for: VARIANTS CMH4 LYS-258; HIS-809; GLN-819 AND HIS-872.
[19]	"Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy." Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B., Komajda M. Circulation 107:2227-2232(2003) [PubMed: 12707239] [Abstract] Cited for: VARIANTS CMH4 PRO-257; LYS-258; GLU-278; ALA-279; PRO-352; TRP-501; LYS-503 DEL; GLN-541; ARG-810; VAL-832; THR-1193 AND THR-1254, VARIANTS GLN-326 AND MET-895.
[20]	Erratum Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B., Komajda M. Circulation 109:3258-3258(2004)
[21]	"Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy." Erdmann J., Daehmlow S., Wischke S., Senyuva M., Werner U., Raible J., Tanis N., Dyachenko S., Hummel M., Hetzer R., Regitz-Zagrosek V. Clin. Genet. 64:339-349(2003) [PubMed: 12974739] [Abstract] Cited for: VARIANTS CMH4 LYS-258; TRP-282; ARG-506; TRP-522; ARG-565; PRO-667; VAL-832 AND ILE-1114, VARIANTS GLY-236 AND GLN-326.
[22]	"The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands." Alders M., Jongbloed R., Deelen W., van den Wijngaard A., Doevendans P., Ten Cate F., Regitz-Zagrosek V., Vosberg H.-P., van Langen I., Wilde A., Dooijes D., Mannens M. Eur. Heart J. 24:1848-1853(2003) [PubMed: 14563344] [Abstract] Cited for: VARIANTS CMH4 SER-161; LYS-258; ASN-604; THR-832; TRP-833 AND THR-1130.
[23]	"A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients." Konno T., Shimizu M., Ino H., Matsuyama T., Yamaguchi M., Terai H., Hayashi K., Mabuchi T., Kiyama M., Sakata K., Hayashi T., Inoue M., Kaneda T., Mabuchi H. J. Am. Coll. Cardiol. 41:781-786(2003) [PubMed: 12628722] [Abstract] Cited for: VARIANT CMH4 GLN-819.
[24]	"Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden." Moerner S., Richard P., Kazzam E., Hellman U., Hainque B., Schwartz K., Waldenstroem A. J. Mol. Cell. Cardiol. 35:841-849(2003) [PubMed: 12818575] [Abstract] Cited for: VARIANTS CMH4 SER-237; HIS-667 AND THR-832, VARIANTS GLN-326 AND MET-895.
[25]	"Genetic and phenotypic characterization of mutations in myosin-binding protein C (MYBPC3) in 81 families with familial hypertrophic cardiomyopathy: total or partial haploinsufficiency." Andersen P.S., Havndrup O., Bundgaard H., Larsen L.A., Vuust J., Pedersen A.K., Kjeldsen K., Christiansen M. Eur. J. Hum. Genet. 12:673-677(2004) [PubMed: 15114369] [Abstract] Cited for: VARIANTS CMH4 ASN-228; LYS-258; LYS-812 DEL AND THR-832.
[26]	"Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy." Van Driest S.L., Vasile V.C., Ommen S.R., Will M.L., Tajik A.J., Gersh B.J., Ackerman M.J. J. Am. Coll. Cardiol. 44:1903-1910(2004) [PubMed: 15519027] [Abstract] Cited for: VARIANTS CMH4 ARG-5; LEU-219; ILE-256; LYS-258; HIS-457; ARG-489; GLN-494; TRP-501; GLN-541; VAL-603; ASN-604; LEU-607; CYS-732; ASN-769; ARG-791; HIS-809; LYS-810 DEL; THR-832; GLU-997; ARG-997; ILE-1112 AND THR-1130, VARIANTS MET-158; GLY-236; GLN-326; TRP-382; SER-415; ARG-506; MET-544 AND MET-895.
[27]	"Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy." Hayashi T., Arimura T., Itoh-Satoh M., Ueda K., Hohda S., Inagaki N., Takahashi M., Hori H., Yasunami M., Nishi H., Koga Y., Nakamura H., Matsuzaki M., Choi B.Y., Bae S.W., You C.W., Han K.H., Park J.E. , Knoell R., Hoshijima M., Chien K.R., Kimura A. J. Am. Coll. Cardiol. 44:2192-2201(2004) [PubMed: 15582318] [Abstract] Cited for: VARIANT GLY-236.
[28]	"Mutations profile in Chinese patients with hypertrophic cardiomyopathy." Song L., Zou Y., Wang J., Wang Z., Zhen Y., Lou K., Zhang Q., Wang X., Wang H., Li J., Hui R. Clin. Chim. Acta 351:209-216(2005) [PubMed: 15563892] [Abstract] Cited for: VARIANTS CMH4 LYS-258; ARG-263; SER-416; HIS-668 AND ASP-758.
[29]	"Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling." Ingles J., Doolan A., Chiu C., Seidman J., Seidman C., Semsarian C. J. Med. Genet. 42:E59-E59(2005) [PubMed: 16199542] [Abstract] Cited for: VARIANTS CMH4 HIS-273; TRP-501 AND GLN-541, VARIANT GLN-326.
[30]	"Shared genetic causes of cardiac hypertrophy in children and adults." Morita H., Rehm H.L., Menesses A., McDonough B., Roberts A.E., Kucherlapati R., Towbin J.A., Seidman J.G., Seidman C.E. N. Engl. J. Med. 358:1899-1908(2008) [PubMed: 18403758] [Abstract] Cited for: VARIANTS CMH4 GLU-278; ARG-489; GLY-494; GLN-501; TRP-501; ASN-604; SER-1027 AND ARG-1247, VARIANTS MET-158; GLY-236; GLN-326; MET-895 AND TRP-1001.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X84075 mRNA. Translation: CAA58882.1.
Y10129 Genomic DNA. Translation: CAA71216.1.
U91629 Genomic DNA. Translation: AAC04620.1.
AY518390 Genomic DNA. Translation: AAR89909.1.
S80778 mRNA. Translation: AAB35662.1.

IPI

IPI00798035.

PIR

S55050.

RefSeq

NP_000247.2. NM_000256.3.

UniGene

Hs.524906.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GXE	NMR	-	A	640-769	[»]
1PD6	NMR	-	A	358-450	[»]
2AVG	NMR	-	A	151-260	[»]
2K1M	NMR	-	A	2-96	[»]
2V6H	X-ray	1.55	A	151-258	[»]
3CX2	X-ray	1.30	A	151-258	[»]

ProteinModelPortal

Q14896.

SMR

Q14896. Positions 2-96, 151-258, 358-1270.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14896. 1 interaction.

MINT

MINT-6174801.

STRING

Q14896.

PTM databases

PhosphoSite

Q14896.

Polymorphism databases

DMDM

116242668.

2D gel databases

UCD-2DPAGE

Q14896.

Proteomic databases

PRIDE

Q14896.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256993; ENSP00000256993; ENSG00000134571.

GeneID

4607.

KEGG

hsa:4607.

Organism-specific databases

CTD

4607.

GeneCards

GC11M047309.

H-InvDB

HIX0201800.

HGNC

HGNC:7551. MYBPC3.

MIM

115197. phenotype.
600958. gene.

neXtProt

NX_Q14896.

Orphanet

154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
54260. Left ventricular noncompaction.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19375.

GeneTree

ENSGT00600000084284.

HOVERGEN

HBG052560.

OrthoDB

EOG4H462X.

Enzyme and pathway databases

Reactome

REACT_17044. Muscle contraction.

Gene expression databases

ArrayExpress

Q14896.

Bgee

Q14896.

CleanEx

HS_MYBPC3.

Genevestigator

Q14896.

GermOnline

ENSG00000134571. Homo sapiens.

Family and domain databases

InterPro

IPR003961. Fibronectin_type3.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 12 hits.

KO

K12568.

Pfam

PF00041. fn3. 3 hits.
PF07679. I-set. 8 hits.
[Graphical view]

SMART

SM00060. FN3. 3 hits.
SM00409. IG. 7 hits.
SM00408. IGc2. 1 hit.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 3 hits.

PROSITE

PS50853. FN3. 3 hits.
PS50835. IG_LIKE. 6 hits.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

MYPC3_HUMAN

Accession

Primary (citable) accession number: Q14896
Secondary accession number(s): Q16410 , Q6R2F7, Q9UE27, Q9UM53

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 125 of the entry and version 3 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.