MYLK4_HUMAN
ID MYLK4_HUMAN Reviewed; 388 AA.
AC Q86YV6; A2RUC0; Q5TAW2;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Myosin light chain kinase family member 4;
DE EC=2.7.11.1;
DE AltName: Full=Sugen kinase 85;
DE Short=SgK085;
GN Name=MYLK4; Synonyms=SGK085;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-50.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 234-388 (ISOFORM 2).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION.
RX PubMed=12471243; DOI=10.1126/science.1075762;
RA Manning G., Whyte D.B., Martinez R., Hunter T., Sudarsanam S.;
RT "The protein kinase complement of the human genome.";
RL Science 298:1912-1934(2002).
RN [5]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-30; ARG-50; SER-78; MET-126; LEU-217;
RP TYR-318 AND ARG-373.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- INTERACTION:
CC Q86YV6; P08238: HSP90AB1; NbExp=3; IntAct=EBI-6424604, EBI-352572;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86YV6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86YV6-2; Sequence=VSP_026948;
CC -!- MISCELLANEOUS: [Isoform 2]: Sequence incomplete. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AL138876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132831; AAI32832.1; -; mRNA.
DR EMBL; BC132833; AAI32834.1; -; mRNA.
DR EMBL; AK122581; BAC56922.1; -; mRNA.
DR CCDS; CCDS34330.1; -. [Q86YV6-1]
DR RefSeq; NP_001012418.2; NM_001012418.4. [Q86YV6-1]
DR RefSeq; NP_001334801.1; NM_001347872.1.
DR RefSeq; XP_005249136.1; XM_005249079.2. [Q86YV6-1]
DR RefSeq; XP_016866308.1; XM_017010819.1.
DR PDB; 2X4F; X-ray; 2.67 A; A/B=40-388.
DR PDBsum; 2X4F; -.
DR AlphaFoldDB; Q86YV6; -.
DR SMR; Q86YV6; -.
DR BioGRID; 131005; 21.
DR IntAct; Q86YV6; 79.
DR STRING; 9606.ENSP00000274643; -.
DR BindingDB; Q86YV6; -.
DR ChEMBL; CHEMBL5426; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q86YV6; -.
DR PhosphoSitePlus; Q86YV6; -.
DR BioMuta; MYLK4; -.
DR DMDM; 118573873; -.
DR jPOST; Q86YV6; -.
DR MassIVE; Q86YV6; -.
DR MaxQB; Q86YV6; -.
DR PaxDb; Q86YV6; -.
DR PeptideAtlas; Q86YV6; -.
DR PRIDE; Q86YV6; -.
DR ProteomicsDB; 70476; -. [Q86YV6-1]
DR Antibodypedia; 9246; 135 antibodies from 24 providers.
DR DNASU; 340156; -.
DR Ensembl; ENST00000274643.9; ENSP00000274643.7; ENSG00000145949.11. [Q86YV6-1]
DR GeneID; 340156; -.
DR KEGG; hsa:340156; -.
DR MANE-Select; ENST00000274643.9; ENSP00000274643.7; NM_001012418.5; NP_001012418.2.
DR UCSC; uc003mty.5; human. [Q86YV6-1]
DR CTD; 340156; -.
DR DisGeNET; 340156; -.
DR GeneCards; MYLK4; -.
DR HGNC; HGNC:27972; MYLK4.
DR HPA; ENSG00000145949; Group enriched (skeletal muscle, tongue).
DR neXtProt; NX_Q86YV6; -.
DR OpenTargets; ENSG00000145949; -.
DR PharmGKB; PA162396406; -.
DR VEuPathDB; HostDB:ENSG00000145949; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000156211; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q86YV6; -.
DR OrthoDB; 218222at2759; -.
DR PhylomeDB; Q86YV6; -.
DR TreeFam; TF314166; -.
DR PathwayCommons; Q86YV6; -.
DR SignaLink; Q86YV6; -.
DR BioGRID-ORCS; 340156; 13 hits in 1105 CRISPR screens.
DR ChiTaRS; MYLK4; human.
DR EvolutionaryTrace; Q86YV6; -.
DR GenomeRNAi; 340156; -.
DR Pharos; Q86YV6; Tchem.
DR PRO; PR:Q86YV6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q86YV6; protein.
DR Bgee; ENSG00000145949; Expressed in biceps brachii and 113 other tissues.
DR ExpressionAtlas; Q86YV6; baseline and differential.
DR Genevisible; Q86YV6; HS.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004687; F:myosin light chain kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase;
KW Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..388
FT /note="Myosin light chain kinase family member 4"
FT /id="PRO_0000261030"
FT DOMAIN 106..361
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 227
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 112..120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 135
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 234..252
FT /note="LCVNRDAKQIKIIDFGLAR -> QCSRFLIDTSILPLCLLNC (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_026948"
FT VARIANT 30
FT /note="E -> Q (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040864"
FT VARIANT 39
FT /note="E -> A (in dbSNP:rs7770402)"
FT /id="VAR_051650"
FT VARIANT 50
FT /note="G -> R (in dbSNP:rs2296356)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_040865"
FT VARIANT 78
FT /note="A -> S (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation; dbSNP:rs762093504)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040866"
FT VARIANT 126
FT /note="T -> M (in dbSNP:rs34953021)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040867"
FT VARIANT 217
FT /note="H -> L (in a lung squamous cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040868"
FT VARIANT 318
FT /note="C -> Y (in dbSNP:rs35609073)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040869"
FT VARIANT 373
FT /note="Q -> R (in dbSNP:rs35211631)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040870"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:2X4F"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 131..138
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 142..155
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 189..194
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 201..220
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:2X4F"
FT TURN 238..241
FT /evidence="ECO:0007829|PDB:2X4F"
FT STRAND 242..245
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 282..298
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 308..317
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 332..339
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 352..357
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 359..362
FT /evidence="ECO:0007829|PDB:2X4F"
FT HELIX 364..372
FT /evidence="ECO:0007829|PDB:2X4F"
SQ SEQUENCE 388 AA; 44508 MW; EF710F6145DFC3C9 CRC64;
MLKVKRLEEF NTCYNSNQLE KMAFFQCREE VEKVKCFLEK NSGDQDSRSG HNEAKEVWSN
ADLTERMPVK SKRTSALAVD IPAPPAPFDH RIVTAKQGAV NSFYTVSKTE ILGGGRFGQV
HKCEETATGL KLAAKIIKTR GMKDKEEVKN EISVMNQLDH ANLIQLYDAF ESKNDIVLVM
EYVDGGELFD RIIDESYNLT ELDTILFMKQ ICEGIRHMHQ MYILHLDLKP ENILCVNRDA
KQIKIIDFGL ARRYKPREKL KVNFGTPEFL APEVVNYDFV SFPTDMWSVG VIAYMLLSGL
SPFLGDNDAE TLNNILACRW DLEDEEFQDI SEEAKEFISK LLIKEKSWRI SASEALKHPW
LSDHKLHSRL NAQKKKNRGS DAQDFVTK
