ML12B_HUMAN
ID ML12B_HUMAN Reviewed; 172 AA.
AC O14950; D3DUH6; Q13182; Q7Z5Z4;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Myosin regulatory light chain 12B;
DE AltName: Full=MLC-2A;
DE Short=MLC-2;
DE AltName: Full=Myosin regulatory light chain 2-B, smooth muscle isoform;
DE AltName: Full=Myosin regulatory light chain 20 kDa;
DE Short=MLC20;
DE AltName: Full=Myosin regulatory light chain MRLC2;
DE AltName: Full=SHUJUN-1;
GN Name=MYL12B; Synonyms=MRLC2, MYLC2B;
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], PHOSPHORYLATION AT THR-19 AND SER-20, AND
RP MUTAGENESIS OF 19-THR-SER-20.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11436981; DOI=10.1540/jsmr.37.25;
RA Watanabe M., Kohri M., Takaishi M., Horie R., Higashihara M.;
RT "Molecular cloning and sequencing of myosin light chains in human
RT megakaryoblastic leukemia cells.";
RL J. Smooth Muscle Res. 37:25-38(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Fujiwara T., Kawai A., Shimizu F., Shinomiya K., Hirano H., Okuno S.,
RA Ozaki K., Katagiri T., Takeda S., Kuga Y., Shimada Y., Nagata M.,
RA Takaichi A., Watanabe T., Horie M., Nakamura Y., Takahashi E., Hirai Y.;
RT "Molecular cloning of a novel human myosin regulatory light chain.";
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Brodie S.G., Rubin S.E., Montoya G.D., Garry P.J., Williams T.M.;
RT "Human myosin regulatory light chain cDNA homologous to the rat myosin
RT regulatory light chain B (MLC-B).";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Nasopharyngeal carcinoma;
RA Shu J., Li G., He X.;
RT "Construction of cDNA expression library from nasopharyngeal carcinoma
RT tissue and screening of antigenic genes.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [9]
RP FUNCTION.
RX PubMed=10965042; DOI=10.1093/oxfordjournals.jbchem.a022771;
RA Suizu F., Ueda K., Iwasaki T., Murata-Hori M., Hosoya H.;
RT "Activation of actin-activated MgATPase activity of myosin II by
RT phosphorylation with MAPK-activated protein kinase-1b (RSK-2).";
RL J. Biochem. 128:435-440(2000).
RN [10]
RP PHOSPHORYLATION AT THR-19 AND SER-20, AND MUTAGENESIS OF 19-THR-SER-20.
RX PubMed=12429016; DOI=10.1042/bj20021559;
RA Fumoto K., Uchimura T., Iwasaki T., Ueda K., Hosoya H.;
RT "Phosphorylation of myosin II regulatory light chain is necessary for
RT migration of HeLa cells but not for localization of myosin II at the
RT leading edge.";
RL Biochem. J. 370:551-556(2003).
RN [11]
RP MUTAGENESIS OF 19-THR-SER-20.
RX PubMed=12589046; DOI=10.1091/mbc.e02-04-0214;
RA Duran J.M., Valderrama F., Castel S., Magdalena J., Tomas M., Hosoya H.,
RA Renau-Piqueras J., Malhotra V., Egea G.;
RT "Myosin motors and not actin comets are mediators of the actin-based Golgi-
RT to-endoplasmic reticulum protein transport.";
RL Mol. Biol. Cell 14:445-459(2003).
RN [12]
RP PHOSPHORYLATION AT THR-19 AND SER-20.
RX PubMed=15946647; DOI=10.1016/j.bbrc.2005.05.108;
RA Umeda D., Tachibana H., Yamada K.;
RT "Epigallocatechin-3-O-gallate disrupts stress fibers and the contractile
RT ring by reducing myosin regulatory light chain phosphorylation mediated
RT through the target molecule 67 kDa laminin receptor.";
RL Biochem. Biophys. Res. Commun. 333:628-635(2005).
RN [13]
RP PHOSPHORYLATION BY ZIPK/DAPK3.
RX PubMed=17126281; DOI=10.1016/j.abb.2006.09.026;
RA Takamoto N., Komatsu S., Komaba S., Niiro N., Ikebe M.;
RT "Novel ZIP kinase isoform lacks leucine zipper.";
RL Arch. Biochem. Biophys. 456:194-203(2006).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=18480596; DOI=10.1540/jsmr.44.29;
RA Higashihara M., Watanabe M., Usuda S., Miyazaki K.;
RT "Smooth muscle type isoform of 20 kDa myosin light chain is expressed in
RT monocyte/macrophage cell lineage.";
RL J. Smooth Muscle Res. 44:29-40(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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. Phosphorylation triggers actin
CC polymerization in vascular smooth muscle. Implicated in cytokinesis,
CC receptor capping, and cell locomotion. {ECO:0000269|PubMed:10965042}.
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:Q3THE2}.
CC -!- INTERACTION:
CC O14950; P60709: ACTB; NbExp=3; IntAct=EBI-1642165, EBI-353944;
CC O14950; P35749: MYH11; NbExp=2; IntAct=EBI-1642165, EBI-1052928;
CC O14950; Q6X4W1-2: NSMF; NbExp=3; IntAct=EBI-1642165, EBI-12028784;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in various hematopoietic
CC cells. {ECO:0000269|PubMed:11436981, ECO:0000269|PubMed:18480596}.
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 reduced following epigallocatechin-3-O-gallate
CC treatment. {ECO:0000269|PubMed:11942626, ECO:0000269|PubMed:12429016,
CC ECO:0000269|PubMed:15946647, ECO:0000269|PubMed:17126281}.
CC -!- MISCELLANEOUS: This chain binds calcium. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP73808.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D82058; BAB88918.1; -; mRNA.
DR EMBL; AB046614; BAB62403.1; -; mRNA.
DR EMBL; D50372; BAA23323.1; -; mRNA.
DR EMBL; U26162; AAA67367.1; -; mRNA.
DR EMBL; AY320408; AAP73808.1; ALT_FRAME; mRNA.
DR EMBL; AK291726; BAF84415.1; -; mRNA.
DR EMBL; CH471113; EAX01675.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01676.1; -; Genomic_DNA.
DR EMBL; CH471113; EAX01677.1; -; Genomic_DNA.
DR EMBL; BC004994; AAH04994.1; -; mRNA.
DR CCDS; CCDS11831.1; -.
DR RefSeq; NP_001138416.1; NM_001144944.1.
DR RefSeq; NP_001138417.1; NM_001144945.1.
DR RefSeq; NP_001289978.1; NM_001303049.1.
DR RefSeq; NP_291024.1; NM_033546.3.
DR AlphaFoldDB; O14950; -.
DR SMR; O14950; -.
DR BioGRID; 125182; 96.
DR IntAct; O14950; 42.
DR MINT; O14950; -.
DR STRING; 9606.ENSP00000463559; -.
DR ChEMBL; CHEMBL4295652; -.
DR iPTMnet; O14950; -.
DR MetOSite; O14950; -.
DR PhosphoSitePlus; O14950; -.
DR SwissPalm; O14950; -.
DR BioMuta; MYL12B; -.
DR EPD; O14950; -.
DR jPOST; O14950; -.
DR MassIVE; O14950; -.
DR MaxQB; O14950; -.
DR PaxDb; O14950; -.
DR PeptideAtlas; O14950; -.
DR PRIDE; O14950; -.
DR ProteomicsDB; 48333; -.
DR TopDownProteomics; O14950; -.
DR Antibodypedia; 21913; 191 antibodies from 24 providers.
DR DNASU; 10627; -.
DR Ensembl; ENST00000237500.10; ENSP00000237500.5; ENSG00000118680.14.
DR Ensembl; ENST00000400175.9; ENSP00000383037.5; ENSG00000118680.14.
DR Ensembl; ENST00000581193.5; ENSP00000463559.1; ENSG00000118680.14.
DR Ensembl; ENST00000584539.1; ENSP00000464464.1; ENSG00000118680.14.
DR Ensembl; ENST00000648965.1; ENSP00000496809.1; ENSG00000118680.14.
DR GeneID; 103910; -.
DR GeneID; 10627; -.
DR KEGG; hsa:103910; -.
DR MANE-Select; ENST00000237500.10; ENSP00000237500.5; NM_033546.4; NP_291024.1.
DR UCSC; uc002klt.5; human.
DR CTD; 103910; -.
DR CTD; 10627; -.
DR DisGeNET; 103910; -.
DR DisGeNET; 10627; -.
DR GeneCards; MYL12B; -.
DR HGNC; HGNC:29827; MYL12B.
DR HPA; ENSG00000118680; Low tissue specificity.
DR neXtProt; NX_O14950; -.
DR OpenTargets; ENSG00000118680; -.
DR PharmGKB; PA164723274; -.
DR VEuPathDB; HostDB:ENSG00000118680; -.
DR eggNOG; KOG0031; Eukaryota.
DR GeneTree; ENSGT00940000153607; -.
DR HOGENOM; CLU_061288_9_3_1; -.
DR InParanoid; O14950; -.
DR OMA; MIQEEHL; -.
DR OrthoDB; 1435392at2759; -.
DR PhylomeDB; O14950; -.
DR TreeFam; TF314218; -.
DR PathwayCommons; O14950; -.
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 SignaLink; O14950; -.
DR SIGNOR; O14950; -.
DR BioGRID-ORCS; 103910; 32 hits in 1014 CRISPR screens.
DR BioGRID-ORCS; 10627; 89 hits in 1019 CRISPR screens.
DR ChiTaRS; MYL12B; human.
DR Pharos; O14950; Tbio.
DR PRO; PR:O14950; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O14950; protein.
DR Bgee; ENSG00000118680; Expressed in gingival epithelium and 197 other tissues.
DR Genevisible; O14950; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0005903; C:brush border; IEA:Ensembl.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:0008360; P:regulation of cell shape; IEA:Ensembl.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR015070; EF_hand_DJBP.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF08976; EF-hand_11; 1.
DR Pfam; PF13405; EF-hand_6; 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 Calcium; Metal-binding; Motor protein; Muscle protein; Myosin;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..172
FT /note="Myosin regulatory light chain 12B"
FT /id="PRO_0000349364"
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 19
FT /note="Phosphothreonine; by MLCK and ZIPK/DAPK3"
FT /evidence="ECO:0000269|PubMed:11942626,
FT ECO:0000269|PubMed:12429016, ECO:0000269|PubMed:15946647"
FT MOD_RES 20
FT /note="Phosphoserine; by MLCK and ZIPK/DAPK3"
FT /evidence="ECO:0000269|PubMed:11942626,
FT ECO:0000269|PubMed:12429016, ECO:0000269|PubMed:15946647"
FT VARIANT 141
FT /note="E -> G (in dbSNP:rs14720)"
FT /id="VAR_046371"
FT MUTAGEN 19..20
FT /note="TS->AA: Shows a decrease in the number of actin
FT filament bundles."
FT /evidence="ECO:0000269|PubMed:11942626,
FT ECO:0000269|PubMed:12429016, ECO:0000269|PubMed:12589046"
FT MUTAGEN 19..20
FT /note="TS->DD: Shows a larger number of actin filament
FT bundles."
FT /evidence="ECO:0000269|PubMed:11942626,
FT ECO:0000269|PubMed:12429016, ECO:0000269|PubMed:12589046"
FT CONFLICT 72
FT /note="A -> V (in Ref. 5; AAP73808)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="M -> T (in Ref. 5; AAP73808)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="R -> G (in Ref. 5; AAP73808)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="E -> G (in Ref. 3; BAA23323)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 172 AA; 19779 MW; 78FF911630F3870B CRC64;
MSSKKAKTKT TKKRPQRATS NVFAMFDQSQ IQEFKEAFNM IDQNRDGFID KEDLHDMLAS
LGKNPTDAYL DAMMNEAPGP INFTMFLTMF GEKLNGTDPE DVIRNAFACF DEEATGTIQE
DYLRELLTTM GDRFTDEEVD ELYREAPIDK KGNFNYIEFT RILKHGAKDK DD
