ST17A_HUMAN
ID ST17A_HUMAN Reviewed; 414 AA.
AC Q9UEE5; A4D1V6; Q8IVC8;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Serine/threonine-protein kinase 17A;
DE EC=2.7.11.1;
DE AltName: Full=DAP kinase-related apoptosis-inducing protein kinase 1;
GN Name=STK17A; Synonyms=DRAK1;
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], FUNCTION, SUBCELLULAR LOCATION,
RP AUTOPHOSPHORYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-90, AND VARIANT
RP GLU-362.
RC TISSUE=Liver, and Placenta;
RX PubMed=9786912; DOI=10.1074/jbc.273.44.29066;
RA Sanjo H., Kawai T., Akira S.;
RT "DRAKs, novel serine/threonine kinases related to death-associated protein
RT kinase that trigger apoptosis.";
RL J. Biol. Chem. 273:29066-29071(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-362.
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-362.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-362.
RC TISSUE=Colon, 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INDUCTION.
RX PubMed=15940259; DOI=10.1038/sj.onc.1208755;
RA Kerley-Hamilton J.S., Pike A.M., Li N., DiRenzo J., Spinella M.J.;
RT "A p53-dominant transcriptional response to cisplatin in testicular germ
RT cell tumor-derived human embryonal carcinoma.";
RL Oncogene 24:6090-6100(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=21802008; DOI=10.1016/j.chembiol.2011.05.010;
RA Miduturu C.V., Deng X., Kwiatkowski N., Yang W., Brault L.,
RA Filippakopoulos P., Chung E., Yang Q., Schwaller J., Knapp S., King R.W.,
RA Lee J.D., Herrgard S., Zarrinkar P., Gray N.S.;
RT "High-throughput kinase profiling: a more efficient approach toward the
RT discovery of new kinase inhibitors.";
RL Chem. Biol. 18:868-879(2011).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=21489989; DOI=10.1074/jbc.m111.218040;
RA Mao P., Hever M.P., Niemaszyk L.M., Haghkerdar J.M., Yanco E.G., Desai D.,
RA Beyrouthy M.J., Kerley-Hamilton J.S., Freemantle S.J., Spinella M.J.;
RT "Serine/threonine kinase 17A is a novel p53 target gene and modulator of
RT cisplatin toxicity and reactive oxygen species in testicular cancer
RT cells.";
RL J. Biol. Chem. 286:19381-19391(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13 AND SER-28, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-126; THR-167; GLN-286 AND GLU-362.
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 -!- FUNCTION: Acts as a positive regulator of apoptosis. Also acts as a
CC regulator of cellular reactive oxygen species.
CC {ECO:0000269|PubMed:21489989, ECO:0000269|PubMed:9786912}.
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 -!- ACTIVITY REGULATION: Inhibited by thiazolidinedione-type compounds:
CC inhibited by furan- and pyridone- thiazolidinediones.
CC {ECO:0000269|PubMed:21802008}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9786912}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta. Lower levels in
CC heart, lung, skeletal muscle, kidney and pancreas.
CC {ECO:0000269|PubMed:9786912}.
CC -!- INDUCTION: Directly regulated by p53/TP53: induced following cisplatin
CC treatment in a p53/TP53-dependent manner. p53/TP53 activates expression
CC by directly binding to its regulatory regions.
CC {ECO:0000269|PubMed:15940259, ECO:0000269|PubMed:21489989}.
CC -!- PTM: Autophosphorylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. DAP kinase subfamily. {ECO:0000305}.
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DR EMBL; AB011420; BAA34126.1; -; mRNA.
DR EMBL; CH236951; EAL24008.1; -; Genomic_DNA.
DR EMBL; AC005189; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093645; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471073; EAW94162.1; -; Genomic_DNA.
DR EMBL; BC023508; AAH23508.2; -; mRNA.
DR EMBL; BC047696; AAH47696.1; -; mRNA.
DR CCDS; CCDS5470.1; -.
DR RefSeq; NP_004751.2; NM_004760.2.
DR PDB; 7QUE; X-ray; 2.40 A; A/B=50-322.
DR PDB; 7QUF; X-ray; 2.60 A; A/B=50-322.
DR PDBsum; 7QUE; -.
DR PDBsum; 7QUF; -.
DR AlphaFoldDB; Q9UEE5; -.
DR SMR; Q9UEE5; -.
DR BioGRID; 114685; 6.
DR IntAct; Q9UEE5; 4.
DR STRING; 9606.ENSP00000319192; -.
DR BindingDB; Q9UEE5; -.
DR ChEMBL; CHEMBL4525; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9UEE5; -.
DR GuidetoPHARMACOLOGY; 2214; -.
DR iPTMnet; Q9UEE5; -.
DR PhosphoSitePlus; Q9UEE5; -.
DR BioMuta; STK17A; -.
DR DMDM; 317373279; -.
DR EPD; Q9UEE5; -.
DR jPOST; Q9UEE5; -.
DR MassIVE; Q9UEE5; -.
DR MaxQB; Q9UEE5; -.
DR PaxDb; Q9UEE5; -.
DR PeptideAtlas; Q9UEE5; -.
DR PRIDE; Q9UEE5; -.
DR ProteomicsDB; 84141; -.
DR Antibodypedia; 13168; 342 antibodies from 41 providers.
DR DNASU; 9263; -.
DR Ensembl; ENST00000319357.6; ENSP00000319192.5; ENSG00000164543.7.
DR Ensembl; ENST00000648544.1; ENSP00000497301.1; ENSG00000164543.7.
DR GeneID; 9263; -.
DR KEGG; hsa:9263; -.
DR MANE-Select; ENST00000319357.6; ENSP00000319192.5; NM_004760.3; NP_004751.2.
DR UCSC; uc003tih.4; human.
DR CTD; 9263; -.
DR DisGeNET; 9263; -.
DR GeneCards; STK17A; -.
DR HGNC; HGNC:11395; STK17A.
DR HPA; ENSG00000164543; Low tissue specificity.
DR MIM; 604726; gene.
DR neXtProt; NX_Q9UEE5; -.
DR OpenTargets; ENSG00000164543; -.
DR PharmGKB; PA36203; -.
DR VEuPathDB; HostDB:ENSG00000164543; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000154014; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q9UEE5; -.
DR OMA; ACRAWNK; -.
DR OrthoDB; 1156450at2759; -.
DR PhylomeDB; Q9UEE5; -.
DR TreeFam; TF314166; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q9UEE5; -.
DR SignaLink; Q9UEE5; -.
DR SIGNOR; Q9UEE5; -.
DR BioGRID-ORCS; 9263; 14 hits in 1111 CRISPR screens.
DR ChiTaRS; STK17A; human.
DR GenomeRNAi; 9263; -.
DR Pharos; Q9UEE5; Tchem.
DR PRO; PR:Q9UEE5; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UEE5; protein.
DR Bgee; ENSG00000164543; Expressed in lymph node and 194 other tissues.
DR Genevisible; Q9UEE5; HS.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR CDD; cd14197; STKc_DRAK1; 1.
DR InterPro; IPR042704; DRAK1_STKc.
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; Apoptosis; ATP-binding; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..414
FT /note="Serine/threonine-protein kinase 17A"
FT /id="PRO_0000086704"
FT DOMAIN 61..321
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 342..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 186
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 67..75
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 126
FT /note="E -> D (in dbSNP:rs56286238)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041145"
FT VARIANT 167
FT /note="M -> T (in dbSNP:rs35940029)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041146"
FT VARIANT 286
FT /note="E -> Q (in dbSNP:rs3779062)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_032823"
FT VARIANT 362
FT /note="K -> E (in dbSNP:rs1044141)"
FT /evidence="ECO:0000269|PubMed:12690205,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9786912, ECO:0000269|Ref.4"
FT /id="VAR_019991"
FT MUTAGEN 90
FT /note="K->A: Loss of activity and of apoptotic function."
FT /evidence="ECO:0000269|PubMed:9786912"
SQ SEQUENCE 414 AA; 46558 MW; E2140290492C2A10 CRC64;
MIPLEKPGSG GSSPGATSGS GRAGRGLSGP CRPPPPPQAR GLLTEIRAVV RTEPFQDGYS
LCPGRELGRG KFAVVRKCIK KDSGKEFAAK FMRKRRKGQD CRMEIIHEIA VLELAQDNPW
VINLHEVYET ASEMILVLEY AAGGEIFDQC VADREEAFKE KDVQRLMRQI LEGVHFLHTR
DVVHLDLKPQ NILLTSESPL GDIKIVDFGL SRILKNSEEL REIMGTPEYV APEILSYDPI
SMATDMWSIG VLTYVMLTGI SPFLGNDKQE TFLNISQMNL SYSEEEFDVL SESAVDFIRT
LLVKKPEDRA TAEECLKHPW LTQSSIQEPS FRMEKALEEA NALQEGHSVP EINSDTDKSE
TKESIVTEEL IVVTSYTLGQ CRQSEKEKME QKAISKRFKF EEPLLQEIPG EFIY
