Full text data of MYH14
MYH14
(KIAA2034)
[Confidence: low (only semi-automatic identification from reviews)]
Myosin-14 (Myosin heavy chain 14; Myosin heavy chain, non-muscle IIc; Non-muscle myosin heavy chain IIc; NMHC II-C)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Myosin-14 (Myosin heavy chain 14; Myosin heavy chain, non-muscle IIc; Non-muscle myosin heavy chain IIc; NMHC II-C)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q7Z406
ID MYH14_HUMAN Reviewed; 1995 AA.
AC Q7Z406; B0I1S2; C3TTN4; Q5CZ75; Q6XYE4; Q76B62; Q8WV23; Q96I22;
read moreAC Q9BT27; Q9BW35; Q9H882;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 2.
DT 22-JAN-2014, entry version 102.
DE RecName: Full=Myosin-14;
DE AltName: Full=Myosin heavy chain 14;
DE AltName: Full=Myosin heavy chain, non-muscle IIc;
DE AltName: Full=Non-muscle myosin heavy chain IIc;
DE Short=NMHC II-C;
GN Name=MYH14; Synonyms=KIAA2034; ORFNames=FP17425;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Sciatic nerve;
RX PubMed=12909352; DOI=10.1016/S0378-1119(03)00613-9;
RA Leal A., Endele S., Stengel C., Huehne K., Loetterle J., Barrantes R.,
RA Winterpacht A., Rautenstrauss B.;
RT "A novel myosin heavy chain gene in human chromosome 19q13.3.";
RL Gene 312:165-171(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Nagase T., Kikuno R., Yamakawa H., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human.";
RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-11; 190-204; 343-353; 403-413; 434-445; 607-613;
RP 669-675; 718-726; 839-845; 899-906; 957-963; 984-990; 1105-1115;
RP 1244-1264; 1469-1478; 1553-1562 AND 1686-1693, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.;
RL Submitted (NOV-2006) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-998 AND 1740-1995
RP (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1297-1995
RP (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1297-1995
RP (ISOFORM 5), AND NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-477
RP (ISOFORM 6).
RC TISSUE=Colon, Lung, Muscle, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 590-773 (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=19240025; DOI=10.1074/jbc.M806574200;
RA Jana S.S., Kim K.Y., Mao J., Kawamoto S., Sellers J.R.,
RA Adelstein R.S.;
RT "An alternatively spliced isoform of non-muscle myosin II-C is not
RT regulated by myosin light chain phosphorylation.";
RL J. Biol. Chem. 284:11563-11571(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 964-1995 (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1335-1995 (ISOFORM 1).
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1431-1995 (ISOFORM 1).
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP IDENTIFICATION.
RX PubMed=11919279;
RA Desjardins P.R., Burkman J.M., Shrager J.B., Allmond L.A.,
RA Stedman H.H.;
RT "Evolutionary implications of three novel members of the human
RT sarcomeric myosin heavy chain gene family.";
RL Mol. Biol. Evol. 19:375-393(2002).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=14594953; DOI=10.1074/jbc.M309981200;
RA Golomb E., Ma X., Jana S.S., Preston Y.A., Kawamoto S., Shoham N.G.,
RA Goldin E., Conti M.A., Sellers J.R., Adelstein R.S.;
RT "Identification and characterization of nonmuscle myosin II-C, a new
RT member of the myosin II family.";
RL J. Biol. Chem. 279:2800-2808(2004).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1969 AND SER-1989, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP VARIANTS DFNA4A CYS-376; SER-726 AND PHE-976, AND VARIANTS VAL-266 AND
RP SER-1559.
RX PubMed=15015131; DOI=10.1086/383285;
RA Donaudy F., Snoeckx R., Pfister M., Zenner H.-P., Blin N.,
RA Di Stazio M., Ferrara A., Lanzara C., Ficarella R., Declau F.,
RA Pusch C.M., Nuernberg P., Melchionda S., Zelante L., Ballana E.,
RA Estivill X., Van Camp G., Gasparini P., Savoia A.;
RT "Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and
RT mutated in patients affected by autosomal dominant hearing impairment
RT (DFNA4).";
RL Am. J. Hum. Genet. 74:770-776(2004).
RN [16]
RP VARIANT DFNA4A LEU-120.
RX PubMed=16222661; DOI=10.1002/ajmg.a.30989;
RA Yang T., Pfister M., Blin N., Zenner H.P., Pusch C.M., Smith R.J.H.;
RT "Genetic heterogeneity of deafness phenotypes linked to DFNA4.";
RL Am. J. Med. Genet. A 139:9-12(2005).
RN [17]
RP VARIANT PNMHH LEU-933, AND VARIANT VAL-1154.
RX PubMed=21480433; DOI=10.1002/humu.21488;
RA Choi B.O., Kang S.H., Hyun Y.S., Kanwal S., Park S.W., Koo H.,
RA Kim S.B., Choi Y.C., Yoo J.H., Kim J.W., Park K.D., Choi K.G.,
RA Kim S.J., Zuchner S., Chung K.W.;
RT "A complex phenotype of peripheral neuropathy, myopathy, hoarseness,
RT and hearing loss is linked to an autosomal dominant mutation in
RT MYH14.";
RL Hum. Mutat. 32:669-677(2011).
CC -!- FUNCTION: Cellular myosin that appears to play a role in
CC cytokinesis, cell shape, and specialized functions such as
CC secretion and capping (By similarity).
CC -!- SUBUNIT: Myosin is a hexameric protein that consists of 2 heavy
CC chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2
CC regulatory light chain subunits (MLC-2) (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q7Z406-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z406-2; Sequence=VSP_040881, VSP_040882;
CC Name=4;
CC IsoId=Q7Z406-4; Sequence=VSP_014628;
CC Name=5;
CC IsoId=Q7Z406-5; Sequence=VSP_014629, VSP_014630;
CC Name=6;
CC IsoId=Q7Z406-6; Sequence=VSP_040881;
CC -!- TISSUE SPECIFICITY: High levels of expression are found in brain
CC (highest in corpus callosum), heart, kidney, liver, lung, small
CC intestine, colon and skeletal muscle. Expression is low in organs
CC composed mainly of smooth muscle, such as aorta, uterus and
CC urinary bladder. No detectable expression is found in thymus,
CC spleen, placenta and lymphocytes.
CC -!- DOMAIN: The rodlike tail sequence is highly repetitive, showing
CC cycles of a 28-residue repeat pattern composed of 4 heptapeptides,
CC characteristic for alpha-helical coiled coils (By similarity).
CC -!- DISEASE: Deafness, autosomal dominant, 4A (DFNA4A) [MIM:600652]: A
CC form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner
CC ear, the nerve pathways to the brain, or the area of the brain
CC that receives sound information. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Peripheral neuropathy, myopathy, hoarseness, and hearing
CC loss (PNMHH) [MIM:614369]: A complex phenotype of progressive
CC peripheral neuropathy and distal myopathy, with later onset of
CC hoarseness and hearing loss. Affected individuals develop distal
CC muscle weakness at a mean age of 10.6 years, followed by
CC progressive atrophy of these muscles. The lower limbs are more
CC severely affected than the upper limbs, and the muscle weakness
CC first affects anterior leg muscles and later posterior leg
CC muscles. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SIMILARITY: Contains 1 myosin head-like domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO39147.1; Type=Frameshift; Positions=1017, 1057;
CC Sequence=AAP34449.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAP34449.1; Type=Frameshift; Positions=1016, 1057, 1490, 1755;
CC Sequence=BAB14735.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BG468611; Type=Erroneous termination; Positions=403; Note=Translated as Leu;
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DR EMBL; AY165122; AAO39147.1; ALT_FRAME; mRNA.
DR EMBL; AB111886; BAC98374.1; -; mRNA.
DR EMBL; AB290169; BAG06723.1; -; mRNA.
DR EMBL; AC008655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010515; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC020906; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000676; AAH00676.2; -; mRNA.
DR EMBL; BC004396; AAH04396.1; -; mRNA.
DR EMBL; BC007877; AAH07877.2; -; mRNA.
DR EMBL; BC018933; AAH18933.2; -; mRNA.
DR EMBL; FJ041910; ACM78630.1; -; mRNA.
DR EMBL; BG468611; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY203926; AAP34449.1; ALT_SEQ; mRNA.
DR EMBL; CR936653; CAI56791.1; -; mRNA.
DR EMBL; AK023943; BAB14735.1; ALT_INIT; mRNA.
DR RefSeq; NP_001070654.1; NM_001077186.1.
DR RefSeq; NP_001139281.1; NM_001145809.1.
DR RefSeq; NP_079005.3; NM_024729.3.
DR UniGene; Hs.467142; -.
DR PDB; 2YCU; X-ray; 2.25 A; A=47-799.
DR PDBsum; 2YCU; -.
DR ProteinModelPortal; Q7Z406; -.
DR SMR; Q7Z406; 47-921.
DR DIP; DIP-33170N; -.
DR IntAct; Q7Z406; 11.
DR MINT; MINT-1146777; -.
DR PhosphoSite; Q7Z406; -.
DR DMDM; 71151982; -.
DR PaxDb; Q7Z406; -.
DR PRIDE; Q7Z406; -.
DR Ensembl; ENST00000262269; ENSP00000262269; ENSG00000105357.
DR Ensembl; ENST00000425460; ENSP00000407879; ENSG00000105357.
DR Ensembl; ENST00000596571; ENSP00000472819; ENSG00000105357.
DR Ensembl; ENST00000598205; ENSP00000472543; ENSG00000105357.
DR Ensembl; ENST00000601313; ENSP00000470298; ENSG00000105357.
DR GeneID; 79784; -.
DR KEGG; hsa:79784; -.
DR UCSC; uc002prr.1; human.
DR CTD; 79784; -.
DR GeneCards; GC19P050706; -.
DR H-InvDB; HIX0015356; -.
DR HGNC; HGNC:23212; MYH14.
DR MIM; 600652; phenotype.
DR MIM; 608568; gene.
DR MIM; 614369; phenotype.
DR neXtProt; NX_Q7Z406; -.
DR Orphanet; 90635; Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
DR PharmGKB; PA134935217; -.
DR eggNOG; COG5022; -.
DR HOVERGEN; HBG004704; -.
DR KO; K10352; -.
DR OrthoDB; EOG71CFK3; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; MYH14; human.
DR GeneWiki; MYH14; -.
DR GenomeRNAi; 79784; -.
DR NextBio; 35482592; -.
DR PRO; PR:Q7Z406; -.
DR ArrayExpress; Q7Z406; -.
DR Bgee; Q7Z406; -.
DR Genevestigator; Q7Z406; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0016459; C:myosin complex; IEA:UniProtKB-KW.
DR GO; GO:0001725; C:stress fiber; IEA:Ensembl.
DR GO; GO:0030898; F:actin-dependent ATPase activity; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000146; F:microfilament motor activity; IEA:Ensembl.
DR GO; GO:0030048; P:actin filament-based movement; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR Gene3D; 4.10.270.10; -; 1.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR027401; Myosin-like_IQ_dom.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR002928; Myosin_tail.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00063; Myosin_head; 1.
DR Pfam; PF01576; Myosin_tail_1; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR SMART; SM00015; IQ; 1.
DR SMART; SM00242; MYSc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW ATP-binding; Calmodulin-binding; Cell shape; Coiled coil;
KW Complete proteome; Deafness; Direct protein sequencing;
KW Disease mutation; Motor protein; Myosin; Neuropathy;
KW Non-syndromic deafness; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1995 Myosin-14.
FT /FTId=PRO_0000123431.
FT DOMAIN 17 802 Myosin head-like.
FT DOMAIN 803 832 IQ.
FT NP_BIND 198 205 ATP (Potential).
FT COILED 862 1947 Potential.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 1969 1969 Phosphoserine.
FT MOD_RES 1989 1989 Phosphoserine.
FT VAR_SEQ 231 231 P -> PASVSTVSY (in isoform 2 and isoform
FT 6).
FT /FTId=VSP_040881.
FT VAR_SEQ 640 640 D -> DEHGGFQQFSFLGSFPPSPPGSAERCSSAISPPG
FT (in isoform 2).
FT /FTId=VSP_040882.
FT VAR_SEQ 1317 1532 Missing (in isoform 4).
FT /FTId=VSP_014628.
FT VAR_SEQ 1451 1478 MDLEQQRQLVSTLEKKQRKFDQLLAEEK -> LSPDALTDG
FT AQPPSSLDPTGPCPRNPAL (in isoform 5).
FT /FTId=VSP_014629.
FT VAR_SEQ 1479 1995 Missing (in isoform 5).
FT /FTId=VSP_014630.
FT VARIANT 120 120 S -> L (in DFNA4A).
FT /FTId=VAR_037302.
FT VARIANT 266 266 I -> V.
FT /FTId=VAR_022866.
FT VARIANT 334 334 P -> A (in dbSNP:rs34498817).
FT /FTId=VAR_056176.
FT VARIANT 376 376 G -> C (in DFNA4A).
FT /FTId=VAR_022867.
FT VARIANT 726 726 R -> S (in DFNA4A; dbSNP:rs28940307).
FT /FTId=VAR_022868.
FT VARIANT 933 933 R -> L (in PNMHH).
FT /FTId=VAR_066338.
FT VARIANT 976 976 L -> F (in DFNA4A; dbSNP:rs28940306).
FT /FTId=VAR_022869.
FT VARIANT 1154 1154 A -> V.
FT /FTId=VAR_066339.
FT VARIANT 1209 1209 A -> E (in dbSNP:rs11669191).
FT /FTId=VAR_056177.
FT VARIANT 1540 1540 V -> I (in dbSNP:rs680446).
FT /FTId=VAR_056178.
FT VARIANT 1559 1559 N -> S.
FT /FTId=VAR_022870.
FT CONFLICT 411 411 F -> S (in Ref. 5; BG468611).
FT CONFLICT 444 444 A -> G (in Ref. 5; BG468611).
FT CONFLICT 446 446 A -> D (in Ref. 5; BG468611).
FT CONFLICT 458 458 R -> S (in Ref. 5; BG468611).
FT CONFLICT 466 466 S -> D (in Ref. 5; BG468611).
FT CONFLICT 473 473 F -> L (in Ref. 5; BG468611).
FT CONFLICT 997 997 M -> I (in Ref. 5; AAH18933).
FT HELIX 51 53
FT STRAND 55 60
FT TURN 61 63
FT STRAND 64 73
FT STRAND 75 82
FT TURN 83 85
FT STRAND 88 92
FT HELIX 93 95
FT HELIX 102 104
FT HELIX 110 112
FT HELIX 118 130
FT STRAND 135 138
FT STRAND 141 145
FT HELIX 156 162
FT HELIX 167 169
FT HELIX 174 188
FT STRAND 192 197
FT HELIX 204 218
FT STRAND 222 224
FT STRAND 226 228
FT TURN 237 239
FT HELIX 241 249
FT STRAND 259 270
FT STRAND 276 284
FT HELIX 288 291
FT HELIX 302 310
FT HELIX 313 318
FT HELIX 324 326
FT TURN 338 340
FT HELIX 341 354
FT HELIX 359 374
FT HELIX 375 377
FT STRAND 384 386
FT HELIX 395 403
FT HELIX 408 416
FT STRAND 419 428
FT HELIX 433 463
FT STRAND 471 478
FT STRAND 486 488
FT HELIX 490 510
FT HELIX 512 520
FT HELIX 535 542
FT STRAND 545 547
FT HELIX 550 556
FT STRAND 557 560
FT HELIX 565 576
FT TURN 587 589
FT STRAND 592 598
FT STRAND 601 605
FT HELIX 610 615
FT HELIX 620 627
FT HELIX 632 637
FT HELIX 670 686
FT STRAND 688 696
FT TURN 709 711
FT HELIX 712 719
FT HELIX 721 730
FT STRAND 734 737
FT HELIX 738 745
FT HELIX 746 748
FT TURN 750 752
FT STRAND 771 783
FT HELIX 787 799
SQ SEQUENCE 1995 AA; 227871 MW; C77AAB26817B773B CRC64;
MAAVTMSVPG RKAPPRPGPV PEAAQPFLFT PRGPSAGGGP GSGTSPQVEW TARRLVWVPS
ELHGFEAAAL RDEGEEEAEV ELAESGRRLR LPRDQIQRMN PPKFSKAEDM AELTCLNEAS
VLHNLRERYY SGLIYTYSGL FCVVINPYKQ LPIYTEAIVE MYRGKKRHEV PPHVYAVTEG
AYRSMLQDRE DQSILCTGES GAGKTENTKK VIQYLAHVAS SPKGRKEPGV PGELERQLLQ
ANPILEAFGN AKTVKNDNSS RFGKFIRINF DVAGYIVGAN IETYLLEKSR AIRQAKDECS
FHIFYQLLGG AGEQLKADLL LEPCSHYRFL TNGPSSSPGQ ERELFQETLE SLRVLGFSHE
EIISMLRMVS AVLQFGNIAL KRERNTDQAT MPDNTAAQKL CRLLGLGVTD FSRALLTPRI
KVGRDYVQKA QTKEQADFAL EALAKATYER LFRWLVLRLN RALDRSPRQG ASFLGILDIA
GFEIFQLNSF EQLCINYTNE KLQQLFNHTM FVLEQEEYQR EGIPWTFLDF GLDLQPCIDL
IERPANPPGL LALLDEECWF PKATDKSFVE KVAQEQGGHP KFQRPRHLRD QADFSVLHYA
GKVDYKANEW LMKNMDPLND NVAALLHQST DRLTAEIWKD VEGIVGLEQV SSLGDGPPGG
RPRRGMFRTV GQLYKESLSR LMATLSNTNP SFVRCIVPNH EKRAGKLEPR LVLDQLRCNG
VLEGIRICRQ GFPNRILFQE FRQRYEILTP NAIPKGFMDG KQACEKMIQA LELDPNLYRV
GQSKIFFRAG VLAQLEEERD LKVTDIIVSF QAAARGYLAR RAFQKRQQQQ SALRVMQRNC
AAYLKLRHWQ WWRLFTKVKP LLQVTRQDEV LQARAQELQK VQELQQQSAR EVGELQGRVA
QLEEERARLA EQLRAEAELC AEAEETRGRL AARKQELELV VSELEARVGE EEECSRQMQT
EKKRLQQHIQ ELEAHLEAEE GARQKLQLEK VTTEAKMKKF EEDLLLLEDQ NSKLSKERKL
LEDRLAEFSS QAAEEEEKVK SLNKLRLKYE ATIADMEDRL RKEEKGRQEL EKLKRRLDGE
SSELQEQMVE QQQRAEELRA QLGRKEEELQ AALARAEDEG GARAQLLKSL REAQAALAEA
QEDLESERVA RTKAEKQRRD LGEELEALRG ELEDTLDSTN AQQELRSKRE QEVTELKKTL
EEETRIHEAA VQELRQRHGQ ALGELAEQLE QARRGKGAWE KTRLALEAEV SELRAELSSL
QTARQEGEQR RRRLELQLQE VQGRAGDGER ARAEAAEKLQ RAQAELENVS GALNEAESKT
IRLSKELSST EAQLHDAQEL LQEETRAKLA LGSRVRAMEA EAAGLREQLE EEAAARERAG
RELQTAQAQL SEWRRRQEEE AGALEAGEEA RRRAAREAEA LTQRLAEKTE TVDRLERGRR
RLQQELDDAT MDLEQQRQLV STLEKKQRKF DQLLAEEKAA VLRAVEERER AEAEGREREA
RALSLTRALE EEQEAREELE RQNRALRAEL EALLSSKDDV GKSVHELERA CRVAEQAAND
LRAQVTELED ELTAAEDAKL RLEVTVQALK TQHERDLQGR DEAGEERRRQ LAKQLRDAEV
ERDEERKQRT LAVAARKKLE GELEELKAQM ASAGQGKEEA VKQLRKMQAQ MKELWREVEE
TRTSREEIFS QNRESEKRLK GLEAEVLRLQ EELAASDRAR RQAQQDRDEM ADEVANGNLS
KAAILEEKRQ LEGRLGQLEE ELEEEQSNSE LLNDRYRKLL LQVESLTTEL SAERSFSAKA
ESGRQQLERQ IQELRGRLGE EDAGARARHK MTIAALESKL AQAEEQLEQE TRERILSGKL
VRRAEKRLKE VVLQVEEERR VADQLRDQLE KGNLRVKQLK RQLEEAEEEA SRAQAGRRRL
QRELEDVTES AESMNREVTT LRNRLRRGPL TFTTRTVRQV FRLEEGVASD EEAEEAQPGS
GPSPEPEGSP PAHPQ
//
ID MYH14_HUMAN Reviewed; 1995 AA.
AC Q7Z406; B0I1S2; C3TTN4; Q5CZ75; Q6XYE4; Q76B62; Q8WV23; Q96I22;
read moreAC Q9BT27; Q9BW35; Q9H882;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 2.
DT 22-JAN-2014, entry version 102.
DE RecName: Full=Myosin-14;
DE AltName: Full=Myosin heavy chain 14;
DE AltName: Full=Myosin heavy chain, non-muscle IIc;
DE AltName: Full=Non-muscle myosin heavy chain IIc;
DE Short=NMHC II-C;
GN Name=MYH14; Synonyms=KIAA2034; ORFNames=FP17425;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Sciatic nerve;
RX PubMed=12909352; DOI=10.1016/S0378-1119(03)00613-9;
RA Leal A., Endele S., Stengel C., Huehne K., Loetterle J., Barrantes R.,
RA Winterpacht A., Rautenstrauss B.;
RT "A novel myosin heavy chain gene in human chromosome 19q13.3.";
RL Gene 312:165-171(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Nagase T., Kikuno R., Yamakawa H., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human.";
RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-11; 190-204; 343-353; 403-413; 434-445; 607-613;
RP 669-675; 718-726; 839-845; 899-906; 957-963; 984-990; 1105-1115;
RP 1244-1264; 1469-1478; 1553-1562 AND 1686-1693, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.;
RL Submitted (NOV-2006) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-998 AND 1740-1995
RP (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1297-1995
RP (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1297-1995
RP (ISOFORM 5), AND NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-477
RP (ISOFORM 6).
RC TISSUE=Colon, Lung, Muscle, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 590-773 (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=19240025; DOI=10.1074/jbc.M806574200;
RA Jana S.S., Kim K.Y., Mao J., Kawamoto S., Sellers J.R.,
RA Adelstein R.S.;
RT "An alternatively spliced isoform of non-muscle myosin II-C is not
RT regulated by myosin light chain phosphorylation.";
RL J. Biol. Chem. 284:11563-11571(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 964-1995 (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1335-1995 (ISOFORM 1).
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1431-1995 (ISOFORM 1).
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP IDENTIFICATION.
RX PubMed=11919279;
RA Desjardins P.R., Burkman J.M., Shrager J.B., Allmond L.A.,
RA Stedman H.H.;
RT "Evolutionary implications of three novel members of the human
RT sarcomeric myosin heavy chain gene family.";
RL Mol. Biol. Evol. 19:375-393(2002).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=14594953; DOI=10.1074/jbc.M309981200;
RA Golomb E., Ma X., Jana S.S., Preston Y.A., Kawamoto S., Shoham N.G.,
RA Goldin E., Conti M.A., Sellers J.R., Adelstein R.S.;
RT "Identification and characterization of nonmuscle myosin II-C, a new
RT member of the myosin II family.";
RL J. Biol. Chem. 279:2800-2808(2004).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1969 AND SER-1989, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP VARIANTS DFNA4A CYS-376; SER-726 AND PHE-976, AND VARIANTS VAL-266 AND
RP SER-1559.
RX PubMed=15015131; DOI=10.1086/383285;
RA Donaudy F., Snoeckx R., Pfister M., Zenner H.-P., Blin N.,
RA Di Stazio M., Ferrara A., Lanzara C., Ficarella R., Declau F.,
RA Pusch C.M., Nuernberg P., Melchionda S., Zelante L., Ballana E.,
RA Estivill X., Van Camp G., Gasparini P., Savoia A.;
RT "Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and
RT mutated in patients affected by autosomal dominant hearing impairment
RT (DFNA4).";
RL Am. J. Hum. Genet. 74:770-776(2004).
RN [16]
RP VARIANT DFNA4A LEU-120.
RX PubMed=16222661; DOI=10.1002/ajmg.a.30989;
RA Yang T., Pfister M., Blin N., Zenner H.P., Pusch C.M., Smith R.J.H.;
RT "Genetic heterogeneity of deafness phenotypes linked to DFNA4.";
RL Am. J. Med. Genet. A 139:9-12(2005).
RN [17]
RP VARIANT PNMHH LEU-933, AND VARIANT VAL-1154.
RX PubMed=21480433; DOI=10.1002/humu.21488;
RA Choi B.O., Kang S.H., Hyun Y.S., Kanwal S., Park S.W., Koo H.,
RA Kim S.B., Choi Y.C., Yoo J.H., Kim J.W., Park K.D., Choi K.G.,
RA Kim S.J., Zuchner S., Chung K.W.;
RT "A complex phenotype of peripheral neuropathy, myopathy, hoarseness,
RT and hearing loss is linked to an autosomal dominant mutation in
RT MYH14.";
RL Hum. Mutat. 32:669-677(2011).
CC -!- FUNCTION: Cellular myosin that appears to play a role in
CC cytokinesis, cell shape, and specialized functions such as
CC secretion and capping (By similarity).
CC -!- SUBUNIT: Myosin is a hexameric protein that consists of 2 heavy
CC chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2
CC regulatory light chain subunits (MLC-2) (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q7Z406-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z406-2; Sequence=VSP_040881, VSP_040882;
CC Name=4;
CC IsoId=Q7Z406-4; Sequence=VSP_014628;
CC Name=5;
CC IsoId=Q7Z406-5; Sequence=VSP_014629, VSP_014630;
CC Name=6;
CC IsoId=Q7Z406-6; Sequence=VSP_040881;
CC -!- TISSUE SPECIFICITY: High levels of expression are found in brain
CC (highest in corpus callosum), heart, kidney, liver, lung, small
CC intestine, colon and skeletal muscle. Expression is low in organs
CC composed mainly of smooth muscle, such as aorta, uterus and
CC urinary bladder. No detectable expression is found in thymus,
CC spleen, placenta and lymphocytes.
CC -!- DOMAIN: The rodlike tail sequence is highly repetitive, showing
CC cycles of a 28-residue repeat pattern composed of 4 heptapeptides,
CC characteristic for alpha-helical coiled coils (By similarity).
CC -!- DISEASE: Deafness, autosomal dominant, 4A (DFNA4A) [MIM:600652]: A
CC form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner
CC ear, the nerve pathways to the brain, or the area of the brain
CC that receives sound information. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Peripheral neuropathy, myopathy, hoarseness, and hearing
CC loss (PNMHH) [MIM:614369]: A complex phenotype of progressive
CC peripheral neuropathy and distal myopathy, with later onset of
CC hoarseness and hearing loss. Affected individuals develop distal
CC muscle weakness at a mean age of 10.6 years, followed by
CC progressive atrophy of these muscles. The lower limbs are more
CC severely affected than the upper limbs, and the muscle weakness
CC first affects anterior leg muscles and later posterior leg
CC muscles. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SIMILARITY: Contains 1 myosin head-like domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO39147.1; Type=Frameshift; Positions=1017, 1057;
CC Sequence=AAP34449.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAP34449.1; Type=Frameshift; Positions=1016, 1057, 1490, 1755;
CC Sequence=BAB14735.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BG468611; Type=Erroneous termination; Positions=403; Note=Translated as Leu;
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DR EMBL; AY165122; AAO39147.1; ALT_FRAME; mRNA.
DR EMBL; AB111886; BAC98374.1; -; mRNA.
DR EMBL; AB290169; BAG06723.1; -; mRNA.
DR EMBL; AC008655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010515; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC020906; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000676; AAH00676.2; -; mRNA.
DR EMBL; BC004396; AAH04396.1; -; mRNA.
DR EMBL; BC007877; AAH07877.2; -; mRNA.
DR EMBL; BC018933; AAH18933.2; -; mRNA.
DR EMBL; FJ041910; ACM78630.1; -; mRNA.
DR EMBL; BG468611; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY203926; AAP34449.1; ALT_SEQ; mRNA.
DR EMBL; CR936653; CAI56791.1; -; mRNA.
DR EMBL; AK023943; BAB14735.1; ALT_INIT; mRNA.
DR RefSeq; NP_001070654.1; NM_001077186.1.
DR RefSeq; NP_001139281.1; NM_001145809.1.
DR RefSeq; NP_079005.3; NM_024729.3.
DR UniGene; Hs.467142; -.
DR PDB; 2YCU; X-ray; 2.25 A; A=47-799.
DR PDBsum; 2YCU; -.
DR ProteinModelPortal; Q7Z406; -.
DR SMR; Q7Z406; 47-921.
DR DIP; DIP-33170N; -.
DR IntAct; Q7Z406; 11.
DR MINT; MINT-1146777; -.
DR PhosphoSite; Q7Z406; -.
DR DMDM; 71151982; -.
DR PaxDb; Q7Z406; -.
DR PRIDE; Q7Z406; -.
DR Ensembl; ENST00000262269; ENSP00000262269; ENSG00000105357.
DR Ensembl; ENST00000425460; ENSP00000407879; ENSG00000105357.
DR Ensembl; ENST00000596571; ENSP00000472819; ENSG00000105357.
DR Ensembl; ENST00000598205; ENSP00000472543; ENSG00000105357.
DR Ensembl; ENST00000601313; ENSP00000470298; ENSG00000105357.
DR GeneID; 79784; -.
DR KEGG; hsa:79784; -.
DR UCSC; uc002prr.1; human.
DR CTD; 79784; -.
DR GeneCards; GC19P050706; -.
DR H-InvDB; HIX0015356; -.
DR HGNC; HGNC:23212; MYH14.
DR MIM; 600652; phenotype.
DR MIM; 608568; gene.
DR MIM; 614369; phenotype.
DR neXtProt; NX_Q7Z406; -.
DR Orphanet; 90635; Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
DR PharmGKB; PA134935217; -.
DR eggNOG; COG5022; -.
DR HOVERGEN; HBG004704; -.
DR KO; K10352; -.
DR OrthoDB; EOG71CFK3; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; MYH14; human.
DR GeneWiki; MYH14; -.
DR GenomeRNAi; 79784; -.
DR NextBio; 35482592; -.
DR PRO; PR:Q7Z406; -.
DR ArrayExpress; Q7Z406; -.
DR Bgee; Q7Z406; -.
DR Genevestigator; Q7Z406; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0016459; C:myosin complex; IEA:UniProtKB-KW.
DR GO; GO:0001725; C:stress fiber; IEA:Ensembl.
DR GO; GO:0030898; F:actin-dependent ATPase activity; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000146; F:microfilament motor activity; IEA:Ensembl.
DR GO; GO:0030048; P:actin filament-based movement; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR Gene3D; 4.10.270.10; -; 1.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR027401; Myosin-like_IQ_dom.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR002928; Myosin_tail.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00063; Myosin_head; 1.
DR Pfam; PF01576; Myosin_tail_1; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR SMART; SM00015; IQ; 1.
DR SMART; SM00242; MYSc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW ATP-binding; Calmodulin-binding; Cell shape; Coiled coil;
KW Complete proteome; Deafness; Direct protein sequencing;
KW Disease mutation; Motor protein; Myosin; Neuropathy;
KW Non-syndromic deafness; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1995 Myosin-14.
FT /FTId=PRO_0000123431.
FT DOMAIN 17 802 Myosin head-like.
FT DOMAIN 803 832 IQ.
FT NP_BIND 198 205 ATP (Potential).
FT COILED 862 1947 Potential.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 1969 1969 Phosphoserine.
FT MOD_RES 1989 1989 Phosphoserine.
FT VAR_SEQ 231 231 P -> PASVSTVSY (in isoform 2 and isoform
FT 6).
FT /FTId=VSP_040881.
FT VAR_SEQ 640 640 D -> DEHGGFQQFSFLGSFPPSPPGSAERCSSAISPPG
FT (in isoform 2).
FT /FTId=VSP_040882.
FT VAR_SEQ 1317 1532 Missing (in isoform 4).
FT /FTId=VSP_014628.
FT VAR_SEQ 1451 1478 MDLEQQRQLVSTLEKKQRKFDQLLAEEK -> LSPDALTDG
FT AQPPSSLDPTGPCPRNPAL (in isoform 5).
FT /FTId=VSP_014629.
FT VAR_SEQ 1479 1995 Missing (in isoform 5).
FT /FTId=VSP_014630.
FT VARIANT 120 120 S -> L (in DFNA4A).
FT /FTId=VAR_037302.
FT VARIANT 266 266 I -> V.
FT /FTId=VAR_022866.
FT VARIANT 334 334 P -> A (in dbSNP:rs34498817).
FT /FTId=VAR_056176.
FT VARIANT 376 376 G -> C (in DFNA4A).
FT /FTId=VAR_022867.
FT VARIANT 726 726 R -> S (in DFNA4A; dbSNP:rs28940307).
FT /FTId=VAR_022868.
FT VARIANT 933 933 R -> L (in PNMHH).
FT /FTId=VAR_066338.
FT VARIANT 976 976 L -> F (in DFNA4A; dbSNP:rs28940306).
FT /FTId=VAR_022869.
FT VARIANT 1154 1154 A -> V.
FT /FTId=VAR_066339.
FT VARIANT 1209 1209 A -> E (in dbSNP:rs11669191).
FT /FTId=VAR_056177.
FT VARIANT 1540 1540 V -> I (in dbSNP:rs680446).
FT /FTId=VAR_056178.
FT VARIANT 1559 1559 N -> S.
FT /FTId=VAR_022870.
FT CONFLICT 411 411 F -> S (in Ref. 5; BG468611).
FT CONFLICT 444 444 A -> G (in Ref. 5; BG468611).
FT CONFLICT 446 446 A -> D (in Ref. 5; BG468611).
FT CONFLICT 458 458 R -> S (in Ref. 5; BG468611).
FT CONFLICT 466 466 S -> D (in Ref. 5; BG468611).
FT CONFLICT 473 473 F -> L (in Ref. 5; BG468611).
FT CONFLICT 997 997 M -> I (in Ref. 5; AAH18933).
FT HELIX 51 53
FT STRAND 55 60
FT TURN 61 63
FT STRAND 64 73
FT STRAND 75 82
FT TURN 83 85
FT STRAND 88 92
FT HELIX 93 95
FT HELIX 102 104
FT HELIX 110 112
FT HELIX 118 130
FT STRAND 135 138
FT STRAND 141 145
FT HELIX 156 162
FT HELIX 167 169
FT HELIX 174 188
FT STRAND 192 197
FT HELIX 204 218
FT STRAND 222 224
FT STRAND 226 228
FT TURN 237 239
FT HELIX 241 249
FT STRAND 259 270
FT STRAND 276 284
FT HELIX 288 291
FT HELIX 302 310
FT HELIX 313 318
FT HELIX 324 326
FT TURN 338 340
FT HELIX 341 354
FT HELIX 359 374
FT HELIX 375 377
FT STRAND 384 386
FT HELIX 395 403
FT HELIX 408 416
FT STRAND 419 428
FT HELIX 433 463
FT STRAND 471 478
FT STRAND 486 488
FT HELIX 490 510
FT HELIX 512 520
FT HELIX 535 542
FT STRAND 545 547
FT HELIX 550 556
FT STRAND 557 560
FT HELIX 565 576
FT TURN 587 589
FT STRAND 592 598
FT STRAND 601 605
FT HELIX 610 615
FT HELIX 620 627
FT HELIX 632 637
FT HELIX 670 686
FT STRAND 688 696
FT TURN 709 711
FT HELIX 712 719
FT HELIX 721 730
FT STRAND 734 737
FT HELIX 738 745
FT HELIX 746 748
FT TURN 750 752
FT STRAND 771 783
FT HELIX 787 799
SQ SEQUENCE 1995 AA; 227871 MW; C77AAB26817B773B CRC64;
MAAVTMSVPG RKAPPRPGPV PEAAQPFLFT PRGPSAGGGP GSGTSPQVEW TARRLVWVPS
ELHGFEAAAL RDEGEEEAEV ELAESGRRLR LPRDQIQRMN PPKFSKAEDM AELTCLNEAS
VLHNLRERYY SGLIYTYSGL FCVVINPYKQ LPIYTEAIVE MYRGKKRHEV PPHVYAVTEG
AYRSMLQDRE DQSILCTGES GAGKTENTKK VIQYLAHVAS SPKGRKEPGV PGELERQLLQ
ANPILEAFGN AKTVKNDNSS RFGKFIRINF DVAGYIVGAN IETYLLEKSR AIRQAKDECS
FHIFYQLLGG AGEQLKADLL LEPCSHYRFL TNGPSSSPGQ ERELFQETLE SLRVLGFSHE
EIISMLRMVS AVLQFGNIAL KRERNTDQAT MPDNTAAQKL CRLLGLGVTD FSRALLTPRI
KVGRDYVQKA QTKEQADFAL EALAKATYER LFRWLVLRLN RALDRSPRQG ASFLGILDIA
GFEIFQLNSF EQLCINYTNE KLQQLFNHTM FVLEQEEYQR EGIPWTFLDF GLDLQPCIDL
IERPANPPGL LALLDEECWF PKATDKSFVE KVAQEQGGHP KFQRPRHLRD QADFSVLHYA
GKVDYKANEW LMKNMDPLND NVAALLHQST DRLTAEIWKD VEGIVGLEQV SSLGDGPPGG
RPRRGMFRTV GQLYKESLSR LMATLSNTNP SFVRCIVPNH EKRAGKLEPR LVLDQLRCNG
VLEGIRICRQ GFPNRILFQE FRQRYEILTP NAIPKGFMDG KQACEKMIQA LELDPNLYRV
GQSKIFFRAG VLAQLEEERD LKVTDIIVSF QAAARGYLAR RAFQKRQQQQ SALRVMQRNC
AAYLKLRHWQ WWRLFTKVKP LLQVTRQDEV LQARAQELQK VQELQQQSAR EVGELQGRVA
QLEEERARLA EQLRAEAELC AEAEETRGRL AARKQELELV VSELEARVGE EEECSRQMQT
EKKRLQQHIQ ELEAHLEAEE GARQKLQLEK VTTEAKMKKF EEDLLLLEDQ NSKLSKERKL
LEDRLAEFSS QAAEEEEKVK SLNKLRLKYE ATIADMEDRL RKEEKGRQEL EKLKRRLDGE
SSELQEQMVE QQQRAEELRA QLGRKEEELQ AALARAEDEG GARAQLLKSL REAQAALAEA
QEDLESERVA RTKAEKQRRD LGEELEALRG ELEDTLDSTN AQQELRSKRE QEVTELKKTL
EEETRIHEAA VQELRQRHGQ ALGELAEQLE QARRGKGAWE KTRLALEAEV SELRAELSSL
QTARQEGEQR RRRLELQLQE VQGRAGDGER ARAEAAEKLQ RAQAELENVS GALNEAESKT
IRLSKELSST EAQLHDAQEL LQEETRAKLA LGSRVRAMEA EAAGLREQLE EEAAARERAG
RELQTAQAQL SEWRRRQEEE AGALEAGEEA RRRAAREAEA LTQRLAEKTE TVDRLERGRR
RLQQELDDAT MDLEQQRQLV STLEKKQRKF DQLLAEEKAA VLRAVEERER AEAEGREREA
RALSLTRALE EEQEAREELE RQNRALRAEL EALLSSKDDV GKSVHELERA CRVAEQAAND
LRAQVTELED ELTAAEDAKL RLEVTVQALK TQHERDLQGR DEAGEERRRQ LAKQLRDAEV
ERDEERKQRT LAVAARKKLE GELEELKAQM ASAGQGKEEA VKQLRKMQAQ MKELWREVEE
TRTSREEIFS QNRESEKRLK GLEAEVLRLQ EELAASDRAR RQAQQDRDEM ADEVANGNLS
KAAILEEKRQ LEGRLGQLEE ELEEEQSNSE LLNDRYRKLL LQVESLTTEL SAERSFSAKA
ESGRQQLERQ IQELRGRLGE EDAGARARHK MTIAALESKL AQAEEQLEQE TRERILSGKL
VRRAEKRLKE VVLQVEEERR VADQLRDQLE KGNLRVKQLK RQLEEAEEEA SRAQAGRRRL
QRELEDVTES AESMNREVTT LRNRLRRGPL TFTTRTVRQV FRLEEGVASD EEAEEAQPGS
GPSPEPEGSP PAHPQ
//
MIM
600652
*RECORD*
*FIELD* NO
600652
*FIELD* TI
#600652 DEAFNESS, AUTOSOMAL DOMINANT 4A; DFNA4A
;;DEAFNESS, AUTOSOMAL DOMINANT 4; DFNA4
read more*FIELD* TX
A number sign (#) is used with this entry because autosomal dominant
nonsyndromic deafness-4A (DFNA4A) is caused by heterozygous mutation in
the MYH14 gene (608568) on chromosome 19q13.33.
DFNA4B (614614), another autosomal dominant nonsyndromic deafness
phenotype mapping to chromosome 19q13, is caused by mutation in the
CEACAM16 gene (614591) at 19q13.32.
CLINICAL FEATURES
Mirghomizadeh et al. (2002) reported a 5-generation German family
segregating nonsyndromic autosomal dominant hearing impairment. Affected
individuals showed a progressive sensorineural hearing impairment,
beginning in the first to the second decade and leading to severe to
profound deafness in the fourth decade of their lives.
MAPPING
Using polymorphic microsatellite markers in a linkage study of a family
segregating autosomal dominant nonsyndromic deafness, Chen et al. (1995)
mapped the disorder locus, which they designated DFNA4, to chromosome
19q13.
In a 5-generation German family segregating nonsyndromic autosomal
dominant hearing impairment, Mirghomizadeh et al. (2002) performed a
genomewide scan with microsatellite polymorphisms and found linkage to
markers in the 19q13.3-q13.4 region. Key recombinations were identified
in the family, reducing the disease-specific haplotype to a 14-cM
interval between markers D19S412 and D19S571. This region showed partial
overlap with the previously reported DFNA4 critical region (Chen et al.
(1995)). The BAX gene (600040) mapped to the disease-specific interval,
but genomic sequencing of the coding regions and exon/intron boundaries
excluded disease-related mutations.
MOLECULAR GENETICS
MYH14 was considered a strong candidate gene for hearing loss because it
was located within the candidate region of the DFNA4 locus defined by
Chen et al. (1995) and Mirghomizadeh et al. (2002). Donaudy et al.
(2004) performed mutation screening of the MYH14 gene in 300
hearing-impaired patients from Italy, Spain, and Belgium, and in a
German kindred linked to DFNA4. They identified 1 nonsense (608568.0001)
and 2 missense (608568.0002-608568.0003) mutations in large pedigrees
linked to DFNA4, as well as a de novo allele in a sporadic case
(608568.0004).
In affected members of a 4-generation German family with autosomal
dominant nonsyndromic hearing loss, Yang et al. (2005) identified a
missense mutation in the MYH14 gene (608568.0005). However, complete
screening of the American family that originally defined the DFNA4 locus
(Chen et al., 1995) revealed no mutations in the coding region of the
MYH14 gene; genotyping of SNPs close to the MYH14 gene excluded it from
the candidate region and defined a 19-Mb interval demarcated by D19S414
and SNP dbSNP rs648298. Yang et al. (2005) concluded that a second gene
associated with autosomal dominant nonsyndromic deafness links to the
DFNA4 locus (see DFNA4B, 614614).
*FIELD* RF
1. Chen, A. H.; Ni, L.; Fukushima, K.; Marietta, J.; O'Neill, M.;
Coucke, P.; Willems, P.; Smith, R. J. H.: Linkage of a gene for dominant
non-syndromic deafness to chromosome 19. Hum. Molec. Genet. 4: 1073-1076,
1995.
2. Donaudy, F.; Snoeckx, R.; Pfister, M.; Zenner, H.-P.; Blin, N.;
Di Stazio, M.; Ferrara, A.; Lanzara, C.; Ficarella, R.; Declau, F.;
Pusch, C. M.; Nurnberg, P.; Melchionda, S.; Zelante, L.; Ballana,
E.; Estivill, X.; Van Camp, G.; Gasparini, P.; Savoia, A.: Nonmuscle
myosin heavy-chain gene MYH14 is expressed in cochlea and mutated
in patients affected by autosomal dominant hearing impairment (DFNA4). Am.
J. Hum. Genet. 74: 770-776, 2004.
3. Mirghomizadeh, F.; Bardtke, B.; Devoto, M.; Pfister, M.; Oeken,
J.; Konig, E.; Vitale, E.; Riccio, A.; De Rienzo, A.; Zenner, H. P.;
Blin, N.: Second family with hearing impairment linked to 19q13 and
refined DFNA4 localisation. Europ. J. Hum. Genet. 10: 95-99, 2002.
4. Yang, T.; Pfister, M.; Blin, N.; Zenner, H. P.; Pusch, C. M.; Smith,
R. J. H.: Genetic heterogeneity of deafness phenotypes linked to
DFNA4. Am. J. Med. Genet. 139A: 9-12, 2005.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Ears];
Hearing loss, sensorineural, progressive
MISCELLANEOUS:
Onset of hearing loss in second decade
MOLECULAR BASIS:
Caused by mutation in the myosin, heavy chain 14, nonmuscle gene (MYH14,
608568.0001)
*FIELD* CN
Joanna S. Amberger - updated: 08/25/2004
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 08/25/2004
*FIELD* CN
Marla J. F. O'Neill - updated: 5/1/2012
Marla J. F. O'Neill - updated: 11/17/2005
Victor A. McKusick - updated: 4/13/2004
Michael B. Petersen - updated: 4/30/2002
Victor A. McKusick - updated: 3/2/1999
*FIELD* CD
Victor A. McKusick: 7/13/1995
*FIELD* ED
carol: 12/04/2012
carol: 5/1/2012
carol: 4/6/2012
terry: 12/2/2008
wwang: 11/21/2005
terry: 11/17/2005
tkritzer: 4/19/2004
terry: 4/13/2004
joanna: 3/18/2004
cwells: 5/2/2002
cwells: 4/30/2002
psherman: 3/8/1999
psherman: 3/4/1999
carol: 3/2/1999
dkim: 10/12/1998
jenny: 6/3/1997
mimadm: 11/3/1995
mark: 7/13/1995
*RECORD*
*FIELD* NO
600652
*FIELD* TI
#600652 DEAFNESS, AUTOSOMAL DOMINANT 4A; DFNA4A
;;DEAFNESS, AUTOSOMAL DOMINANT 4; DFNA4
read more*FIELD* TX
A number sign (#) is used with this entry because autosomal dominant
nonsyndromic deafness-4A (DFNA4A) is caused by heterozygous mutation in
the MYH14 gene (608568) on chromosome 19q13.33.
DFNA4B (614614), another autosomal dominant nonsyndromic deafness
phenotype mapping to chromosome 19q13, is caused by mutation in the
CEACAM16 gene (614591) at 19q13.32.
CLINICAL FEATURES
Mirghomizadeh et al. (2002) reported a 5-generation German family
segregating nonsyndromic autosomal dominant hearing impairment. Affected
individuals showed a progressive sensorineural hearing impairment,
beginning in the first to the second decade and leading to severe to
profound deafness in the fourth decade of their lives.
MAPPING
Using polymorphic microsatellite markers in a linkage study of a family
segregating autosomal dominant nonsyndromic deafness, Chen et al. (1995)
mapped the disorder locus, which they designated DFNA4, to chromosome
19q13.
In a 5-generation German family segregating nonsyndromic autosomal
dominant hearing impairment, Mirghomizadeh et al. (2002) performed a
genomewide scan with microsatellite polymorphisms and found linkage to
markers in the 19q13.3-q13.4 region. Key recombinations were identified
in the family, reducing the disease-specific haplotype to a 14-cM
interval between markers D19S412 and D19S571. This region showed partial
overlap with the previously reported DFNA4 critical region (Chen et al.
(1995)). The BAX gene (600040) mapped to the disease-specific interval,
but genomic sequencing of the coding regions and exon/intron boundaries
excluded disease-related mutations.
MOLECULAR GENETICS
MYH14 was considered a strong candidate gene for hearing loss because it
was located within the candidate region of the DFNA4 locus defined by
Chen et al. (1995) and Mirghomizadeh et al. (2002). Donaudy et al.
(2004) performed mutation screening of the MYH14 gene in 300
hearing-impaired patients from Italy, Spain, and Belgium, and in a
German kindred linked to DFNA4. They identified 1 nonsense (608568.0001)
and 2 missense (608568.0002-608568.0003) mutations in large pedigrees
linked to DFNA4, as well as a de novo allele in a sporadic case
(608568.0004).
In affected members of a 4-generation German family with autosomal
dominant nonsyndromic hearing loss, Yang et al. (2005) identified a
missense mutation in the MYH14 gene (608568.0005). However, complete
screening of the American family that originally defined the DFNA4 locus
(Chen et al., 1995) revealed no mutations in the coding region of the
MYH14 gene; genotyping of SNPs close to the MYH14 gene excluded it from
the candidate region and defined a 19-Mb interval demarcated by D19S414
and SNP dbSNP rs648298. Yang et al. (2005) concluded that a second gene
associated with autosomal dominant nonsyndromic deafness links to the
DFNA4 locus (see DFNA4B, 614614).
*FIELD* RF
1. Chen, A. H.; Ni, L.; Fukushima, K.; Marietta, J.; O'Neill, M.;
Coucke, P.; Willems, P.; Smith, R. J. H.: Linkage of a gene for dominant
non-syndromic deafness to chromosome 19. Hum. Molec. Genet. 4: 1073-1076,
1995.
2. Donaudy, F.; Snoeckx, R.; Pfister, M.; Zenner, H.-P.; Blin, N.;
Di Stazio, M.; Ferrara, A.; Lanzara, C.; Ficarella, R.; Declau, F.;
Pusch, C. M.; Nurnberg, P.; Melchionda, S.; Zelante, L.; Ballana,
E.; Estivill, X.; Van Camp, G.; Gasparini, P.; Savoia, A.: Nonmuscle
myosin heavy-chain gene MYH14 is expressed in cochlea and mutated
in patients affected by autosomal dominant hearing impairment (DFNA4). Am.
J. Hum. Genet. 74: 770-776, 2004.
3. Mirghomizadeh, F.; Bardtke, B.; Devoto, M.; Pfister, M.; Oeken,
J.; Konig, E.; Vitale, E.; Riccio, A.; De Rienzo, A.; Zenner, H. P.;
Blin, N.: Second family with hearing impairment linked to 19q13 and
refined DFNA4 localisation. Europ. J. Hum. Genet. 10: 95-99, 2002.
4. Yang, T.; Pfister, M.; Blin, N.; Zenner, H. P.; Pusch, C. M.; Smith,
R. J. H.: Genetic heterogeneity of deafness phenotypes linked to
DFNA4. Am. J. Med. Genet. 139A: 9-12, 2005.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Ears];
Hearing loss, sensorineural, progressive
MISCELLANEOUS:
Onset of hearing loss in second decade
MOLECULAR BASIS:
Caused by mutation in the myosin, heavy chain 14, nonmuscle gene (MYH14,
608568.0001)
*FIELD* CN
Joanna S. Amberger - updated: 08/25/2004
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 08/25/2004
*FIELD* CN
Marla J. F. O'Neill - updated: 5/1/2012
Marla J. F. O'Neill - updated: 11/17/2005
Victor A. McKusick - updated: 4/13/2004
Michael B. Petersen - updated: 4/30/2002
Victor A. McKusick - updated: 3/2/1999
*FIELD* CD
Victor A. McKusick: 7/13/1995
*FIELD* ED
carol: 12/04/2012
carol: 5/1/2012
carol: 4/6/2012
terry: 12/2/2008
wwang: 11/21/2005
terry: 11/17/2005
tkritzer: 4/19/2004
terry: 4/13/2004
joanna: 3/18/2004
cwells: 5/2/2002
cwells: 4/30/2002
psherman: 3/8/1999
psherman: 3/4/1999
carol: 3/2/1999
dkim: 10/12/1998
jenny: 6/3/1997
mimadm: 11/3/1995
mark: 7/13/1995
MIM
608568
*RECORD*
*FIELD* NO
608568
*FIELD* TI
*608568 MYOSIN, HEAVY CHAIN 14, NONMUSCLE; MYH14
;;NONMUSCLE MYOSIN HEAVY CHAIN IIC;;
read moreNMHC IIC;;
KIAA2034
*FIELD* TX
DESCRIPTION
MYH14 is a member of the nonmuscle myosin II family of ATP-dependent
molecular motors, which interact with cytoskeletal actin and regulate
cytokinesis, cell motility, and cell polarity (Golomb et al., 2004).
CLONING
By sequence analysis and RT-PCR of sciatic nerve RNA, Leal et al. (2003)
cloned MYH14. The deduced 1,995-amino acid protein has a calculated
molecular mass of 228 kD. MYH14 contains an N-terminal myosin domain, a
myosin head region, 2 IQ domains, and a C-terminal myosin tail. It
shares significant similarity with MYH9 (160775), MYH10 (160776), and
MYH11 (160745), with highest conservation in the myosin head domain.
Northern blot analysis detected a 7.0-kb transcript expressed at highest
levels in small intestine, colon, and skeletal muscle. By EST analysis
and RT-PCR of colon and peripheral nerve RNA, Leal et al. (2003)
identified several splice variants resulting from exon skipping and the
use of alternate acceptor and donor sites.
Golomb et al. (2004) cloned mouse and human MYH14 and identified 2
splice variants of each. Northern blot analysis of several human tissues
detected highest expression in skeletal muscle. Expression was also
detected in brain, heart, colon, kidney, liver, small intestine, and
lung, but not in thymus, spleen, placenta, and lymphocytes. RNA dot blot
analysis detected elevated MYH14 expression in corpus callosum. Little
MYH14 was detected in organs composed mainly of smooth muscle, such as
aorta, uterus, and bladder. Human fetal tissues showed little or no
MYH14 expression compared with adult tissues. Immunofluorescent
microscopy of developing mouse embryos revealed Myh14 expression in the
developing sensory area of the cochlea and in the apical area of
intestinal epithelial cells. This pattern of expression differed from
those displayed by Myh9 and Myh10
Choi et al. (2011) demonstrated MYH14 expression in human skeletal
muscle by quantitative real-time PCR.
GENE FUNCTION
By immunoprecipitation of mouse lung proteins, Golomb et al. (2004)
demonstrated that Myh14 forms a homodimer and does not form heterodimers
with either Myh9 or Myh10. Recombinant MYH14, expressed in insect cells,
bound to skeletal muscle actin in the absence of MgATP and was released
in the presence of MgATP.
Kim et al. (2005) found that the mouse Myh14 isoform containing an
8-amino acids insertion in loop 1 had higher MgATPase activity and
supported more rapid in vitro actin-filament sliding activity than the
Myh14 isoform without the insertion.
GENE STRUCTURE
Leal et al. (2003) determined that the MYH14 gene contains 41 exons and
spans 108 kb. Exon 1 is untranslated.
MAPPING
By genomic sequence analysis, Leal et al. (2003) mapped the MYH14 gene
to chromosome 19q13.33. Golomb et al. (2004) mapped the mouse Myh14 gene
to chromosome 7.
MOLECULAR GENETICS
MYH14 was considered a strong candidate gene for hearing loss because it
maps to the same region of chromosome 19 as does a form of autosomal
dominant nonsyndromic sensorineural deafness (DFNA4; 600652), and
because a number of unconventional and conventional myosins are known to
be involved in various forms of hereditary deafness. After demonstrating
that Myh14 is highly expressed in mouse cochlea, Donaudy et al. (2004)
performed mutation screening of the MYH14 gene in a series of 300
hearing-impaired patients from Italy, Spain, and Belgium, and in a
German kindred linked to the DFNA4 region. They identified 1 nonsense
(608568.0001) and 2 missense (608568.0002-608568.0003) mutations in
large pedigrees linked to DFNA4, as well as a de novo allele in a
sporadic case (608568.0004). These mutations were not found in 200
healthy control individuals.
By genomewide linkage analysis followed by candidate gene sequencing of
a large Korean family with autosomal dominant peripheral neuropathy,
myopathy, hoarseness, and hearing loss (PNMHH; 614369), Choi et al.
(2011) identified a heterozygous mutation in the MYH14 gene (R941L;
608568.0006). The phenotype was characterized by onset around age 10
years of progressive distal muscle weakness and atrophy, affecting the
lower limbs more than the upper limbs. Older individuals developed
hoarseness and sensorineural hearing loss. Sensation was not affected,
although most had decreased or absent deep tendon reflexes. Laboratory
studies suggested a myopathic and neurogenic process.
*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, SER7TER
In affected members of a 4-generation German kindred with autosomal
dominant nonsyndromic sensorineural hearing loss (600652) that mapped to
the DFNA4 region of chromosome 19, Donaudy et al. (2004) identified a
20C-A transversion in exon 1 of the MYH14 gene, resulting in a
ser7-to-ter (S7X) change in the motor domain of the protein. Affected
individuals showed progressive sensorineural hearing impairment that
started in the first or second decade of life and led to severe to
profound hearing loss in the fourth decade of life.
.0002
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, LEU976PHE
In affected members of an Italian family with autosomal dominant
nonsyndromic sensorineural hearing loss (600652), Donaudy et al. (2004)
identified heterozygosity for a 2926C-T transition in exon 22 of the
MYH14 gene, resulting in a leu976-to-phe (L976F) change in the tail of
the protein. Affected members in this family had a mild to moderate
bilateral sensorineural hearing impairment without vestibular symptoms.
.0003
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, ARG726SER
In affected members of a large Belgian kindred with autosomal dominant
nonsyndromic sensorineural hearing loss (600652), Donaudy et al. (2004)
identified a 2176C-A transversion in exon 16 of the MYH14 gene,
resulting in an arg726-to-ser (R726S) change in the tail of the protein.
The patients showed a mild to moderate progressive hearing loss without
vestibular involvement.
Kim et al. (2005) found that a mutation homologous to R726S in mouse
Myh14 (R230S) had no effect on its actin-activated MgATPase activity,
but it decreased the rate of actin-filament sliding.
.0004
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, GLY376CYS
In a 9-year-old Italian patient with autosomal dominant nonsyndromic
sensorineural hearing loss (600652), Donaudy et al. (2004) identified a
1126G-T transversion in exon 9 of the MYH14 gene, resulting in a
gly376-to-cys (G376C) change in the motor domain of the protein. The
patient apparently represented a de novo mutation. The patient had a
moderate bilateral sensorineural hearing loss without vestibular
involvement.
.0005
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, SER120LEU
In affected members of a 4-generation German family with autosomal
dominant nonsyndromic hearing loss (600652), Yang et al. (2005)
identified a 466C-T transition in exon 1 of the MYH14 gene, predicting a
ser120-to-leu (S120L) substitution. Audiogram profiles of affected
members were characterized by moderate hearing loss across all
frequencies tested.
.0006
PERIPHERAL NEUROPATHY, MYOPATHY, HOARSENESS, AND HEARING LOSS
MYH14, ARG941LEU
In affected members of a large Korean family with autosomal dominant
inheritance of peripheral neuropathy, myopathy, hoarseness, and hearing
loss (PNMHH; 614369), Choi et al. (2011) identified a heterozygous
2822G-T transversion in the MYH14 gene, resulting in an arg941-to-leu
(R941L) substitution in a highly conserved residue in the tail domain.
The mutation was not found in 566 control chromosomes. The mutation was
found by genomewide linkage analysis followed by candidate gene
sequencing.
*FIELD* RF
1. Choi, B.-O.; Kang, S. H.; Hyun, Y. S.; Kanwal, S.; Park, S. W.;
Koo, H.; Kim, S.-B.; Choi, Y.-C.; Yoo, J. H.; Kim, J.-W.; Park, K.
D.; Choi, K.-G.; Kim, S. J.; Zuchner, S.; Chung, K. W.: A complex
phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing
loss is linked to an autosomal dominant mutation in MYH14. Hum. Mutat. 32:
669-677, 2011.
2. Donaudy, F.; Snoeckx, R.; Pfister, M.; Zenner, H.-P.; Blin, N.;
Di Stazio, M.; Ferrara, A.; Lanzara, C.; Ficarella, R.; Declau, F.;
Pusch, C. M.; Nurnberg, P.; Melchionda, S.; Zelante, L.; Ballana,
E.; Estivill, X.; Van Camp, G.; Gasparini, P.; Savoia, A.: Nonmuscle
myosin heavy-chain gene MYH14 is expressed in cochlea and mutated
in patients affected by autosomal dominant hearing impairment (DFNA4). Am.
J. Hum. Genet. 74: 770-776, 2004.
3. Golomb, E.; Ma, X.; Jana, S. S.; Preston, Y. A.; Kawamoto, S.;
Shoham, N. G.; Goldin, E.; Conti, M. A.; Sellers, J. R.; Adelstein,
R. S.: Identification and characterization of nonmuscle myosin II-C,
a new member of the myosin II family. J. Biol. Chem. 279;-2800-2808,
2004.
4. Kim, K.-Y.; Kovacs, M.; Kawamoto, S.; Sellers, J. R.; Adelstein,
R. S.: Disease-associated mutations and alternative splicing alter
the enzymatic and motile activity of nonmuscle myosins II-B and II-C. J.
Biol. Chem. 280: 22769-22775, 2005.
5. Leal, A.; Endele, S.; Stengel, C.; Huehne, K.; Loetterle, J.; Barrantes,
R.; Winterpacht, A.; Rautenstrauss, B.: A novel myosin heavy chain
gene in human chromosome 19q13.3. Gene 312: 165-171, 2003.
6. Yang, T.; Pfister, M.; Blin, N.; Zenner, H. P.; Pusch, C. M.; Smith,
R. J. H.: Genetic heterogeneity of deafness phenotypes linked to
DFNA4. Am. J. Med. Genet. 139A: 9-12, 2005.
*FIELD* CN
Cassandra L. Kniffin - updated: 11/30/2011
Patricia A. Hartz - updated: 2/9/2006
Marla J. F. O'Neill - updated: 11/17/2005
Victor A. McKusick - updated: 4/13/2004
*FIELD* CD
Patricia A. Hartz: 4/5/2004
*FIELD* ED
carol: 04/06/2012
carol: 12/1/2011
ckniffin: 11/30/2011
terry: 12/2/2008
mgross: 3/9/2006
terry: 2/9/2006
wwang: 11/21/2005
terry: 11/17/2005
tkritzer: 4/19/2004
terry: 4/13/2004
mgross: 4/5/2004
*RECORD*
*FIELD* NO
608568
*FIELD* TI
*608568 MYOSIN, HEAVY CHAIN 14, NONMUSCLE; MYH14
;;NONMUSCLE MYOSIN HEAVY CHAIN IIC;;
read moreNMHC IIC;;
KIAA2034
*FIELD* TX
DESCRIPTION
MYH14 is a member of the nonmuscle myosin II family of ATP-dependent
molecular motors, which interact with cytoskeletal actin and regulate
cytokinesis, cell motility, and cell polarity (Golomb et al., 2004).
CLONING
By sequence analysis and RT-PCR of sciatic nerve RNA, Leal et al. (2003)
cloned MYH14. The deduced 1,995-amino acid protein has a calculated
molecular mass of 228 kD. MYH14 contains an N-terminal myosin domain, a
myosin head region, 2 IQ domains, and a C-terminal myosin tail. It
shares significant similarity with MYH9 (160775), MYH10 (160776), and
MYH11 (160745), with highest conservation in the myosin head domain.
Northern blot analysis detected a 7.0-kb transcript expressed at highest
levels in small intestine, colon, and skeletal muscle. By EST analysis
and RT-PCR of colon and peripheral nerve RNA, Leal et al. (2003)
identified several splice variants resulting from exon skipping and the
use of alternate acceptor and donor sites.
Golomb et al. (2004) cloned mouse and human MYH14 and identified 2
splice variants of each. Northern blot analysis of several human tissues
detected highest expression in skeletal muscle. Expression was also
detected in brain, heart, colon, kidney, liver, small intestine, and
lung, but not in thymus, spleen, placenta, and lymphocytes. RNA dot blot
analysis detected elevated MYH14 expression in corpus callosum. Little
MYH14 was detected in organs composed mainly of smooth muscle, such as
aorta, uterus, and bladder. Human fetal tissues showed little or no
MYH14 expression compared with adult tissues. Immunofluorescent
microscopy of developing mouse embryos revealed Myh14 expression in the
developing sensory area of the cochlea and in the apical area of
intestinal epithelial cells. This pattern of expression differed from
those displayed by Myh9 and Myh10
Choi et al. (2011) demonstrated MYH14 expression in human skeletal
muscle by quantitative real-time PCR.
GENE FUNCTION
By immunoprecipitation of mouse lung proteins, Golomb et al. (2004)
demonstrated that Myh14 forms a homodimer and does not form heterodimers
with either Myh9 or Myh10. Recombinant MYH14, expressed in insect cells,
bound to skeletal muscle actin in the absence of MgATP and was released
in the presence of MgATP.
Kim et al. (2005) found that the mouse Myh14 isoform containing an
8-amino acids insertion in loop 1 had higher MgATPase activity and
supported more rapid in vitro actin-filament sliding activity than the
Myh14 isoform without the insertion.
GENE STRUCTURE
Leal et al. (2003) determined that the MYH14 gene contains 41 exons and
spans 108 kb. Exon 1 is untranslated.
MAPPING
By genomic sequence analysis, Leal et al. (2003) mapped the MYH14 gene
to chromosome 19q13.33. Golomb et al. (2004) mapped the mouse Myh14 gene
to chromosome 7.
MOLECULAR GENETICS
MYH14 was considered a strong candidate gene for hearing loss because it
maps to the same region of chromosome 19 as does a form of autosomal
dominant nonsyndromic sensorineural deafness (DFNA4; 600652), and
because a number of unconventional and conventional myosins are known to
be involved in various forms of hereditary deafness. After demonstrating
that Myh14 is highly expressed in mouse cochlea, Donaudy et al. (2004)
performed mutation screening of the MYH14 gene in a series of 300
hearing-impaired patients from Italy, Spain, and Belgium, and in a
German kindred linked to the DFNA4 region. They identified 1 nonsense
(608568.0001) and 2 missense (608568.0002-608568.0003) mutations in
large pedigrees linked to DFNA4, as well as a de novo allele in a
sporadic case (608568.0004). These mutations were not found in 200
healthy control individuals.
By genomewide linkage analysis followed by candidate gene sequencing of
a large Korean family with autosomal dominant peripheral neuropathy,
myopathy, hoarseness, and hearing loss (PNMHH; 614369), Choi et al.
(2011) identified a heterozygous mutation in the MYH14 gene (R941L;
608568.0006). The phenotype was characterized by onset around age 10
years of progressive distal muscle weakness and atrophy, affecting the
lower limbs more than the upper limbs. Older individuals developed
hoarseness and sensorineural hearing loss. Sensation was not affected,
although most had decreased or absent deep tendon reflexes. Laboratory
studies suggested a myopathic and neurogenic process.
*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, SER7TER
In affected members of a 4-generation German kindred with autosomal
dominant nonsyndromic sensorineural hearing loss (600652) that mapped to
the DFNA4 region of chromosome 19, Donaudy et al. (2004) identified a
20C-A transversion in exon 1 of the MYH14 gene, resulting in a
ser7-to-ter (S7X) change in the motor domain of the protein. Affected
individuals showed progressive sensorineural hearing impairment that
started in the first or second decade of life and led to severe to
profound hearing loss in the fourth decade of life.
.0002
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, LEU976PHE
In affected members of an Italian family with autosomal dominant
nonsyndromic sensorineural hearing loss (600652), Donaudy et al. (2004)
identified heterozygosity for a 2926C-T transition in exon 22 of the
MYH14 gene, resulting in a leu976-to-phe (L976F) change in the tail of
the protein. Affected members in this family had a mild to moderate
bilateral sensorineural hearing impairment without vestibular symptoms.
.0003
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, ARG726SER
In affected members of a large Belgian kindred with autosomal dominant
nonsyndromic sensorineural hearing loss (600652), Donaudy et al. (2004)
identified a 2176C-A transversion in exon 16 of the MYH14 gene,
resulting in an arg726-to-ser (R726S) change in the tail of the protein.
The patients showed a mild to moderate progressive hearing loss without
vestibular involvement.
Kim et al. (2005) found that a mutation homologous to R726S in mouse
Myh14 (R230S) had no effect on its actin-activated MgATPase activity,
but it decreased the rate of actin-filament sliding.
.0004
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, GLY376CYS
In a 9-year-old Italian patient with autosomal dominant nonsyndromic
sensorineural hearing loss (600652), Donaudy et al. (2004) identified a
1126G-T transversion in exon 9 of the MYH14 gene, resulting in a
gly376-to-cys (G376C) change in the motor domain of the protein. The
patient apparently represented a de novo mutation. The patient had a
moderate bilateral sensorineural hearing loss without vestibular
involvement.
.0005
DEAFNESS, AUTOSOMAL DOMINANT 4
MYH14, SER120LEU
In affected members of a 4-generation German family with autosomal
dominant nonsyndromic hearing loss (600652), Yang et al. (2005)
identified a 466C-T transition in exon 1 of the MYH14 gene, predicting a
ser120-to-leu (S120L) substitution. Audiogram profiles of affected
members were characterized by moderate hearing loss across all
frequencies tested.
.0006
PERIPHERAL NEUROPATHY, MYOPATHY, HOARSENESS, AND HEARING LOSS
MYH14, ARG941LEU
In affected members of a large Korean family with autosomal dominant
inheritance of peripheral neuropathy, myopathy, hoarseness, and hearing
loss (PNMHH; 614369), Choi et al. (2011) identified a heterozygous
2822G-T transversion in the MYH14 gene, resulting in an arg941-to-leu
(R941L) substitution in a highly conserved residue in the tail domain.
The mutation was not found in 566 control chromosomes. The mutation was
found by genomewide linkage analysis followed by candidate gene
sequencing.
*FIELD* RF
1. Choi, B.-O.; Kang, S. H.; Hyun, Y. S.; Kanwal, S.; Park, S. W.;
Koo, H.; Kim, S.-B.; Choi, Y.-C.; Yoo, J. H.; Kim, J.-W.; Park, K.
D.; Choi, K.-G.; Kim, S. J.; Zuchner, S.; Chung, K. W.: A complex
phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing
loss is linked to an autosomal dominant mutation in MYH14. Hum. Mutat. 32:
669-677, 2011.
2. Donaudy, F.; Snoeckx, R.; Pfister, M.; Zenner, H.-P.; Blin, N.;
Di Stazio, M.; Ferrara, A.; Lanzara, C.; Ficarella, R.; Declau, F.;
Pusch, C. M.; Nurnberg, P.; Melchionda, S.; Zelante, L.; Ballana,
E.; Estivill, X.; Van Camp, G.; Gasparini, P.; Savoia, A.: Nonmuscle
myosin heavy-chain gene MYH14 is expressed in cochlea and mutated
in patients affected by autosomal dominant hearing impairment (DFNA4). Am.
J. Hum. Genet. 74: 770-776, 2004.
3. Golomb, E.; Ma, X.; Jana, S. S.; Preston, Y. A.; Kawamoto, S.;
Shoham, N. G.; Goldin, E.; Conti, M. A.; Sellers, J. R.; Adelstein,
R. S.: Identification and characterization of nonmuscle myosin II-C,
a new member of the myosin II family. J. Biol. Chem. 279;-2800-2808,
2004.
4. Kim, K.-Y.; Kovacs, M.; Kawamoto, S.; Sellers, J. R.; Adelstein,
R. S.: Disease-associated mutations and alternative splicing alter
the enzymatic and motile activity of nonmuscle myosins II-B and II-C. J.
Biol. Chem. 280: 22769-22775, 2005.
5. Leal, A.; Endele, S.; Stengel, C.; Huehne, K.; Loetterle, J.; Barrantes,
R.; Winterpacht, A.; Rautenstrauss, B.: A novel myosin heavy chain
gene in human chromosome 19q13.3. Gene 312: 165-171, 2003.
6. Yang, T.; Pfister, M.; Blin, N.; Zenner, H. P.; Pusch, C. M.; Smith,
R. J. H.: Genetic heterogeneity of deafness phenotypes linked to
DFNA4. Am. J. Med. Genet. 139A: 9-12, 2005.
*FIELD* CN
Cassandra L. Kniffin - updated: 11/30/2011
Patricia A. Hartz - updated: 2/9/2006
Marla J. F. O'Neill - updated: 11/17/2005
Victor A. McKusick - updated: 4/13/2004
*FIELD* CD
Patricia A. Hartz: 4/5/2004
*FIELD* ED
carol: 04/06/2012
carol: 12/1/2011
ckniffin: 11/30/2011
terry: 12/2/2008
mgross: 3/9/2006
terry: 2/9/2006
wwang: 11/21/2005
terry: 11/17/2005
tkritzer: 4/19/2004
terry: 4/13/2004
mgross: 4/5/2004
MIM
614369
*RECORD*
*FIELD* NO
614369
*FIELD* TI
#614369 PERIPHERAL NEUROPATHY, MYOPATHY, HOARSENESS, AND HEARING LOSS; PNMHH
*FIELD* TX
read moreA number sign (#) is used with this entry because peripheral neuropathy,
myopathy, hoarseness, and hearing loss (PNMHH) is caused by heterozygous
mutation in the MYH14 gene (608568) on chromosome 19q13.
CLINICAL FEATURES
Choi et al. (2011) reported a large 5-generation Korean family with a
complex phenotype of progressive peripheral neuropathy and distal
myopathy, with later onset of hoarseness and hearing loss. Affected
individuals developed distal muscle weakness at a mean age of 10.6
years, followed by progressive atrophy of these muscles. The lower limbs
were more severely affected than the upper limbs, and the muscle
weakness first affected anterior leg muscles and later posterior leg
muscles. Three older patients, around age 40 years, reported proximal
weakness of the thigh muscles. Most patients had foot deformities and a-
or hyporeflexia, although none had sensory loss. Eight (53%) of 15
patients had hoarse voice, but none had dysphagia or vocal cord paresis.
Audiologic studies showed late-onset sensorineural hearing loss in 5
(45%), all of whom were older than 28 years. Serum creatine kinase was
mildly increased only in a few patients. Nerve conduction studies showed
mildly reduced or normal sensory values, but peroneal nerves showed
severely reduced compound motor action potentials (CMAPs). MRI showed
fatty replacement in affected muscles, and muscle biopsies of 2 patients
showed variation of fiber size and shape and subsarcolemmal accumulation
of enlarged mitochondria with variably sized rectangular or elongated
rhomboidal paracrystalline inclusions. The findings were consistent with
both a myopathic and a neuropathic process.
INHERITANCE
The transmission pattern of the disorder in the family reported by Choi
et al. (2011) was compatible with autosomal dominant inheritance.
MAPPING
By genomewide linkage analysis, Choi et al. (2011) found linkage of the
complex phenotype of peripheral neuropathy, myopathy, hoarseness, and
hearing loss in a 5-generation Korean family to chromosome 19q13.3, with
a maximum multipoint lod score of 3.794 at SNP (dbSNP rs1058511) under
an autosomal dominant inheritance model. Fine mapping of the chromosomal
linkage region revealed a 2-point maximum lod score of 6.360 at D19S246.
MOLECULAR GENETICS
By candidate gene sequencing in the 19q13.3 linkage region for the
phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing
loss, Choi et al. (2011) identified a heterozygous mutation in the MYH14
gene (608568.0006).
*FIELD* RF
1. Choi, B.-O.; Kang, S. H.; Hyun, Y. S.; Kanwal, S.; Park, S. W.;
Koo, H.; Kim, S.-B.; Choi, Y.-C.; Yoo, J. H.; Kim, J.-W.; Park, K.
D.; Choi, K.-G.; Kim, S. J.; Zuchner, S.; Chung, K. W.: A complex
phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing
loss is linked to an autosomal dominant mutation in MYH14. Hum. Mutat. 32:
669-677, 2011.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Ears];
Deafness, sensorineural (45%)
SKELETAL:
[Feet];
Foot deformities
MUSCLE, SOFT TISSUE:
Distal muscle weakness (first affects anterior leg muscles, then posterior
leg muscles);
Distal muscle atrophy (lower limbs more affected than upper limbs);
Proximal weakness of the lower limbs with longer disease duration;
MRI shows fatty replacement;
Muscle biopsy shows small rounded fibers;
Degenerating fibers;
Endomysial fibrosis;
Variation of fiber size and shape;
Fiber-type grouping;
Subsarcolemmal accumulation of enlarged mitochondria with variably
sized rectangular or elongated rhomboidal paracrystalline inclusions
NEUROLOGIC:
[Central nervous system];
Tremor (3 patients);
[Peripheral nervous system];
Areflexia;
Hyporeflexia;
Nerve conduction studies show mildly reduced or normal sensory values;
Peroneal nerves show severely reduced CMAPs
VOICE:
Hoarseness (53%)
LABORATORY ABNORMALITIES:
Mildly increased serum creatine kinase
MISCELLANEOUS:
Mean age at onset 10.6 years;
Progressive disorder;
Hearing loss and hoarseness occur later;
One Korean family has been reported (as of November 2011)
MOLECULAR BASIS:
Caused by mutation in the nonmuscle myosin heavy chain 14 gene (MYH14,
608568.0006)
*FIELD* CD
Cassandra L. Kniffin: 11/30/2011
*FIELD* ED
joanna: 12/20/2011
ckniffin: 11/30/2011
*FIELD* CD
Cassandra L. Kniffin: 11/30/2011
*FIELD* ED
carol: 04/06/2012
carol: 12/1/2011
ckniffin: 11/30/2011
*RECORD*
*FIELD* NO
614369
*FIELD* TI
#614369 PERIPHERAL NEUROPATHY, MYOPATHY, HOARSENESS, AND HEARING LOSS; PNMHH
*FIELD* TX
read moreA number sign (#) is used with this entry because peripheral neuropathy,
myopathy, hoarseness, and hearing loss (PNMHH) is caused by heterozygous
mutation in the MYH14 gene (608568) on chromosome 19q13.
CLINICAL FEATURES
Choi et al. (2011) reported a large 5-generation Korean family with a
complex phenotype of progressive peripheral neuropathy and distal
myopathy, with later onset of hoarseness and hearing loss. Affected
individuals developed distal muscle weakness at a mean age of 10.6
years, followed by progressive atrophy of these muscles. The lower limbs
were more severely affected than the upper limbs, and the muscle
weakness first affected anterior leg muscles and later posterior leg
muscles. Three older patients, around age 40 years, reported proximal
weakness of the thigh muscles. Most patients had foot deformities and a-
or hyporeflexia, although none had sensory loss. Eight (53%) of 15
patients had hoarse voice, but none had dysphagia or vocal cord paresis.
Audiologic studies showed late-onset sensorineural hearing loss in 5
(45%), all of whom were older than 28 years. Serum creatine kinase was
mildly increased only in a few patients. Nerve conduction studies showed
mildly reduced or normal sensory values, but peroneal nerves showed
severely reduced compound motor action potentials (CMAPs). MRI showed
fatty replacement in affected muscles, and muscle biopsies of 2 patients
showed variation of fiber size and shape and subsarcolemmal accumulation
of enlarged mitochondria with variably sized rectangular or elongated
rhomboidal paracrystalline inclusions. The findings were consistent with
both a myopathic and a neuropathic process.
INHERITANCE
The transmission pattern of the disorder in the family reported by Choi
et al. (2011) was compatible with autosomal dominant inheritance.
MAPPING
By genomewide linkage analysis, Choi et al. (2011) found linkage of the
complex phenotype of peripheral neuropathy, myopathy, hoarseness, and
hearing loss in a 5-generation Korean family to chromosome 19q13.3, with
a maximum multipoint lod score of 3.794 at SNP (dbSNP rs1058511) under
an autosomal dominant inheritance model. Fine mapping of the chromosomal
linkage region revealed a 2-point maximum lod score of 6.360 at D19S246.
MOLECULAR GENETICS
By candidate gene sequencing in the 19q13.3 linkage region for the
phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing
loss, Choi et al. (2011) identified a heterozygous mutation in the MYH14
gene (608568.0006).
*FIELD* RF
1. Choi, B.-O.; Kang, S. H.; Hyun, Y. S.; Kanwal, S.; Park, S. W.;
Koo, H.; Kim, S.-B.; Choi, Y.-C.; Yoo, J. H.; Kim, J.-W.; Park, K.
D.; Choi, K.-G.; Kim, S. J.; Zuchner, S.; Chung, K. W.: A complex
phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing
loss is linked to an autosomal dominant mutation in MYH14. Hum. Mutat. 32:
669-677, 2011.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Ears];
Deafness, sensorineural (45%)
SKELETAL:
[Feet];
Foot deformities
MUSCLE, SOFT TISSUE:
Distal muscle weakness (first affects anterior leg muscles, then posterior
leg muscles);
Distal muscle atrophy (lower limbs more affected than upper limbs);
Proximal weakness of the lower limbs with longer disease duration;
MRI shows fatty replacement;
Muscle biopsy shows small rounded fibers;
Degenerating fibers;
Endomysial fibrosis;
Variation of fiber size and shape;
Fiber-type grouping;
Subsarcolemmal accumulation of enlarged mitochondria with variably
sized rectangular or elongated rhomboidal paracrystalline inclusions
NEUROLOGIC:
[Central nervous system];
Tremor (3 patients);
[Peripheral nervous system];
Areflexia;
Hyporeflexia;
Nerve conduction studies show mildly reduced or normal sensory values;
Peroneal nerves show severely reduced CMAPs
VOICE:
Hoarseness (53%)
LABORATORY ABNORMALITIES:
Mildly increased serum creatine kinase
MISCELLANEOUS:
Mean age at onset 10.6 years;
Progressive disorder;
Hearing loss and hoarseness occur later;
One Korean family has been reported (as of November 2011)
MOLECULAR BASIS:
Caused by mutation in the nonmuscle myosin heavy chain 14 gene (MYH14,
608568.0006)
*FIELD* CD
Cassandra L. Kniffin: 11/30/2011
*FIELD* ED
joanna: 12/20/2011
ckniffin: 11/30/2011
*FIELD* CD
Cassandra L. Kniffin: 11/30/2011
*FIELD* ED
carol: 04/06/2012
carol: 12/1/2011
ckniffin: 11/30/2011