MYL9_HUMAN
ID MYL9_HUMAN Reviewed; 172 AA.
AC P24844; E1P5T6; Q9BQL9; Q9BUF9; Q9H136;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Myosin regulatory light polypeptide 9;
DE AltName: Full=20 kDa myosin light chain;
DE Short=LC20;
DE AltName: Full=MLC-2C;
DE AltName: Full=Myosin RLC;
DE AltName: Full=Myosin regulatory light chain 2, smooth muscle isoform;
DE AltName: Full=Myosin regulatory light chain 9;
DE AltName: Full=Myosin regulatory light chain MRLC1;
GN Name=MYL9; Synonyms=MLC2, MRLC1, MYRL2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Umbilical artery;
RX PubMed=2526655; DOI=10.1021/bi00435a059;
RA Kumar C.C., Mohan S.R., Zavodny P.J., Narula S.K., Leibowitz P.J.;
RT "Characterization and differential expression of human vascular smooth
RT muscle myosin light chain 2 isoform in nonmuscle cells.";
RL Biochemistry 28:4027-4035(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Pan J.Y., Li S., Silberstein D.S.;
RT "Splice variant of regulatory myosin light chain, short version.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT THR-19 AND
RP SER-20, AND FUNCTION.
RX PubMed=11942626; DOI=10.1247/csf.26.677;
RA Iwasaki T., Murata-Hori M., Ishitobi S., Hosoya H.;
RT "Diphosphorylated MRLC is required for organization of stress fibers in
RT interphase cells and the contractile ring in dividing cells.";
RL Cell Struct. Funct. 26:677-683(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION AT SER-20.
RX PubMed=18854160; DOI=10.1016/j.cell.2008.09.018;
RA Tan I., Yong J., Dong J.M., Lim L., Leung T.;
RT "A tripartite complex containing MRCK modulates lamellar actomyosin
RT retrograde flow.";
RL Cell 135:123-136(2008).
RN [8]
RP PHOSPHORYLATION AT SER-20.
RX PubMed=21072057; DOI=10.1038/cdd.2010.140;
RA Gabet A.S., Coulon S., Fricot A., Vandekerckhove J., Chang Y., Ribeil J.A.,
RA Lordier L., Zermati Y., Asnafi V., Belaid Z., Debili N., Vainchenker W.,
RA Varet B., Hermine O., Courtois G.;
RT "Caspase-activated ROCK-1 allows erythroblast terminal maturation
RT independently of cytokine-induced Rho signaling.";
RL Cell Death Differ. 18:678-689(2011).
RN [9]
RP PHOSPHORYLATION AT THR-19 AND SER-20.
RX PubMed=21457715; DOI=10.1016/j.febslet.2011.03.054;
RA Tan I., Lai J., Yong J., Li S.F., Leung T.;
RT "Chelerythrine perturbs lamellar actomyosin filaments by selective
RT inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase.";
RL FEBS Lett. 585:1260-1268(2011).
RN [10]
RP PHOSPHORYLATION AT SER-20 BY DAPK1; DAPK2 AND ZIPK/DAPK3.
RX PubMed=21408167; DOI=10.1371/journal.pone.0017344;
RA Shoval Y., Berissi H., Kimchi A., Pietrokovski S.;
RT "New modularity of DAP-kinases: alternative splicing of the DRP-1 gene
RT produces a ZIPk-like isoform.";
RL PLoS ONE 6:E17344-E17344(2011).
RN [11]
RP INVOLVEMENT IN MMIHS4.
RX PubMed=29453416; DOI=10.1038/s41431-017-0055-5;
RA Moreno C.A., Sobreira N., Pugh E., Zhang P., Steel G., Torres F.R.,
RA Cavalcanti D.P.;
RT "Homozygous deletion in MYL9 expands the molecular basis of megacystis-
RT microcolon-intestinal hypoperistalsis syndrome.";
RL Eur. J. Hum. Genet. 26:669-675(2018).
RN [12]
RP INVOLVEMENT IN MMIHS4.
RX PubMed=33031641; DOI=10.1002/mgg3.1516;
RA Kandler J.L., Sklirou E., Woerner A., Walsh L., Cox E., Xue Y.;
RT "Compound heterozygous loss of function variants in MYL9 in a child with
RT megacystis-microcolon-intestinal hypoperistalsis syndrome.";
RL Mol. Genet. Genomic Med. 8:e1516-e1516(2020).
CC -!- FUNCTION: Myosin regulatory subunit that plays an important role in
CC regulation of both smooth muscle and nonmuscle cell contractile
CC activity via its phosphorylation. Implicated in cytokinesis, receptor
CC capping, and cell locomotion (PubMed:11942626, PubMed:2526655). In
CC myoblasts, may regulate PIEZO1-dependent cortical actomyosin assembly
CC involved in myotube formation (By similarity).
CC {ECO:0000250|UniProtKB:Q9CQ19, ECO:0000269|PubMed:11942626,
CC ECO:0000269|PubMed:2526655}.
CC -!- SUBUNIT: Myosin is a hexamer of 2 heavy chains and 4 light chains:
CC interacts with myosin heavy chain MYO19.
CC {ECO:0000250|UniProtKB:Q9CQ19}.
CC -!- INTERACTION:
CC P24844-2; A6NI15: MSGN1; NbExp=3; IntAct=EBI-13066228, EBI-11991020;
CC P24844-2; Q99757: TXN2; NbExp=3; IntAct=EBI-13066228, EBI-2932492;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9CQ19}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:Q9CQ19}. Note=Colocalizes with F-actin, MYH9 and
CC PIEZO1 at the actomyosin cortex in myoblasts.
CC {ECO:0000250|UniProtKB:Q9CQ19}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P24844-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P24844-2; Sequence=VSP_042834;
CC -!- TISSUE SPECIFICITY: Smooth muscle tissues and in some, but not all,
CC nonmuscle cells. {ECO:0000269|PubMed:2526655}.
CC -!- PTM: Phosphorylation increases the actin-activated myosin ATPase
CC activity and thereby regulates the contractile activity. It is required
CC to generate the driving force in the migration of the cells but not
CC necessary for localization of myosin-2 at the leading edge.
CC Phosphorylation is required for myotube formation.
CC {ECO:0000250|UniProtKB:P02612, ECO:0000269|PubMed:11942626,
CC ECO:0000269|PubMed:21457715}.
CC -!- DISEASE: Megacystis-microcolon-intestinal hypoperistalsis syndrome 4
CC (MMIHS4) [MIM:619365]: A form of megacystis-microcolon-intestinal
CC hypoperistalsis syndrome, a congenital visceral myopathy primarily
CC affecting females, and characterized by loss of smooth muscle
CC contraction in the bladder and intestine. Affected individuals present
CC at birth with functional obstruction of intestine, microcolon, dilation
CC of bladder, and secondary hydronephrosis. The majority of cases have a
CC fatal outcome due to malnutrition and sepsis, followed by multiorgan
CC failure. MMIHS4 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:29453416, ECO:0000269|PubMed:33031641}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: This chain binds calcium.
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DR EMBL; J02854; AAA59852.1; -; mRNA.
DR EMBL; AF176043; AAQ13654.1; -; mRNA.
DR EMBL; D82057; BAB88917.1; -; mRNA.
DR EMBL; AL050318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76129.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76131.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76132.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76133.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76134.1; -; Genomic_DNA.
DR EMBL; BC002648; AAH02648.1; -; mRNA.
DR CCDS; CCDS13276.1; -. [P24844-1]
DR CCDS; CCDS13277.1; -. [P24844-2]
DR PIR; A32031; A32031.
DR RefSeq; NP_006088.2; NM_006097.4. [P24844-1]
DR RefSeq; NP_852667.1; NM_181526.2. [P24844-2]
DR AlphaFoldDB; P24844; -.
DR SMR; P24844; -.
DR BioGRID; 115670; 51.
DR DIP; DIP-60525N; -.
DR IntAct; P24844; 21.
DR MINT; P24844; -.
DR STRING; 9606.ENSP00000279022; -.
DR iPTMnet; P24844; -.
DR MetOSite; P24844; -.
DR PhosphoSitePlus; P24844; -.
DR BioMuta; MYL9; -.
DR DMDM; 20141521; -.
DR OGP; P24844; -.
DR EPD; P24844; -.
DR jPOST; P24844; -.
DR MassIVE; P24844; -.
DR MaxQB; P24844; -.
DR PaxDb; P24844; -.
DR PeptideAtlas; P24844; -.
DR PRIDE; P24844; -.
DR ProteomicsDB; 54231; -. [P24844-1]
DR ProteomicsDB; 54232; -. [P24844-2]
DR TopDownProteomics; P24844-1; -. [P24844-1]
DR Antibodypedia; 11734; 439 antibodies from 35 providers.
DR DNASU; 10398; -.
DR Ensembl; ENST00000279022.7; ENSP00000279022.2; ENSG00000101335.10. [P24844-1]
DR Ensembl; ENST00000346786.2; ENSP00000217313.2; ENSG00000101335.10. [P24844-2]
DR GeneID; 10398; -.
DR KEGG; hsa:10398; -.
DR MANE-Select; ENST00000279022.7; ENSP00000279022.2; NM_006097.5; NP_006088.2.
DR UCSC; uc002xfl.3; human. [P24844-1]
DR CTD; 10398; -.
DR DisGeNET; 10398; -.
DR GeneCards; MYL9; -.
DR HGNC; HGNC:15754; MYL9.
DR HPA; ENSG00000101335; Tissue enhanced (intestine, urinary bladder).
DR MIM; 609905; gene.
DR MIM; 619365; phenotype.
DR neXtProt; NX_P24844; -.
DR OpenTargets; ENSG00000101335; -.
DR PharmGKB; PA31387; -.
DR VEuPathDB; HostDB:ENSG00000101335; -.
DR eggNOG; KOG0031; Eukaryota.
DR GeneTree; ENSGT00940000155458; -.
DR HOGENOM; CLU_061288_9_3_1; -.
DR InParanoid; P24844; -.
DR OMA; FECFDEN; -.
DR OrthoDB; 1435392at2759; -.
DR PhylomeDB; P24844; -.
DR TreeFam; TF314218; -.
DR PathwayCommons; P24844; -.
DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR Reactome; R-HSA-5625740; RHO GTPases activate PKNs.
DR Reactome; R-HSA-5625900; RHO GTPases activate CIT.
DR Reactome; R-HSA-5627117; RHO GTPases Activate ROCKs.
DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SignaLink; P24844; -.
DR SIGNOR; P24844; -.
DR BioGRID-ORCS; 10398; 14 hits in 1072 CRISPR screens.
DR ChiTaRS; MYL9; human.
DR GeneWiki; MYL9; -.
DR GenomeRNAi; 10398; -.
DR Pharos; P24844; Tbio.
DR PRO; PR:P24844; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P24844; protein.
DR Bgee; ENSG00000101335; Expressed in popliteal artery and 180 other tissues.
DR ExpressionAtlas; P24844; baseline and differential.
DR Genevisible; P24844; HS.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005859; C:muscle myosin complex; TAS:ProtInc.
DR GO; GO:0030016; C:myofibril; IBA:GO_Central.
DR GO; GO:0016460; C:myosin II complex; IBA:GO_Central.
DR GO; GO:0001725; C:stress fiber; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0032036; F:myosin heavy chain binding; IBA:GO_Central.
DR GO; GO:0008307; F:structural constituent of muscle; TAS:ProtInc.
DR GO; GO:0030239; P:myofibril assembly; IBA:GO_Central.
DR GO; GO:0070527; P:platelet aggregation; HMP:UniProtKB.
DR GO; GO:0006937; P:regulation of muscle contraction; TAS:ProtInc.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13405; EF-hand_6; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Calcium; Cytoplasm; Cytoskeleton;
KW Metal-binding; Motor protein; Muscle protein; Myosin; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P29269"
FT CHAIN 2..172
FT /note="Myosin regulatory light polypeptide 9"
FT /id="PRO_0000198735"
FT DOMAIN 29..64
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 98..133
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 134..169
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 44
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 46
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 53
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P29269"
FT MOD_RES 19
FT /note="Phosphothreonine; by MLCK, CIT and ROCK2"
FT /evidence="ECO:0000269|PubMed:11942626,
FT ECO:0000269|PubMed:21457715"
FT MOD_RES 20
FT /note="Phosphoserine; by CDC42BP, CIT, MLCK, PAK1, ROCK1,
FT ROCK2, DAPK1, DAPK2 and ZIPK/DAPK3"
FT /evidence="ECO:0000269|PubMed:11942626,
FT ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21072057,
FT ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:21457715"
FT VAR_SEQ 62..115
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_042834"
FT CONFLICT 10
FT /note="T -> A (in Ref. 1; AAA59852)"
FT /evidence="ECO:0000305"
FT CONFLICT 81
FT /note="I -> Y (in Ref. 1; AAA59852)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="A -> S (in Ref. 1; AAA59852)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="E -> K (in Ref. 1; AAA59852)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="I -> V (in Ref. 1; AAA59852)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="D -> H (in Ref. 1; AAA59852)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 172 AA; 19827 MW; 4C9839E85154CDA8 CRC64;
MSSKRAKAKT TKKRPQRATS NVFAMFDQSQ IQEFKEAFNM IDQNRDGFID KEDLHDMLAS
LGKNPTDEYL EGMMSEAPGP INFTMFLTMF GEKLNGTDPE DVIRNAFACF DEEASGFIHE
DHLRELLTTM GDRFTDEEVD EMYREAPIDK KGNFNYVEFT RILKHGAKDK DD
