STK33_HUMAN
ID STK33_HUMAN Reviewed; 514 AA.
AC Q9BYT3; Q658S6; Q8NEF5;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Serine/threonine-protein kinase 33;
DE EC=2.7.11.1;
GN Name=STK33;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Uterus;
RX PubMed=11738831; DOI=10.1016/s0378-1119(01)00780-6;
RA Mujica A.O., Hankeln T., Schmidt E.R.;
RT "A novel serine/threonine kinase gene, STK33, on human chromosome
RT 11p15.3.";
RL Gene 280:175-181(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 246-514 (ISOFORM 2).
RC TISSUE=Stomach;
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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=16176263; DOI=10.1111/j.1742-4658.2005.04900.x;
RA Mujica A.O., Brauksiepe B., Saaler-Reinhardt S., Reuss S., Schmidt E.R.;
RT "Differential expression pattern of the novel serine/threonine kinase,
RT STK33, in mice and men.";
RL FEBS J. 272:4884-4898(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP FUNCTION.
RX PubMed=21742770; DOI=10.1158/0008-5472.can-11-0778;
RA Babij C., Zhang Y., Kurzeja R.J., Munzli A., Shehabeldin A., Fernando M.,
RA Quon K., Kassner P.D., Ruefli-Brasse A.A., Watson V.J., Fajardo F.,
RA Jackson A., Zondlo J., Sun Y., Ellison A.R., Plewa C.A., San Miguel T.,
RA Robinson J., McCarter J., Schwandner R., Judd T., Carnahan J., Dussault I.;
RT "STk33 kinase activity is non-essential in KRAS-dependent cancer cells.";
RL Cancer Res. 71:5818-5826(2011).
RN [9]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-98; VAL-160; GLU-436; THR-437 AND
RP GLU-458.
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: Serine/threonine protein kinase which phosphorylates VIME.
CC May play a specific role in the dynamic behavior of the intermediate
CC filament cytoskeleton by phosphorylation of VIME (By similarity). Not
CC essential for the survival of KRAS-dependent AML cell lines.
CC {ECO:0000250, ECO:0000269|PubMed:21742770}.
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 -!- SUBUNIT: Interacts with VIME. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BYT3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYT3-2; Sequence=VSP_017939;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, fetal lung and heart,
CC followed by pituitary gland, kidney, interventricular septum, pancreas,
CC heart, trachea, thyroid gland and uterus. Weak hybridization signals
CC were observed in the following tissues: amygdala, aorta, esophagus,
CC colon ascending, colon transverse, skeletal muscle, spleen, peripheral
CC blood leukocyte, lymph node, bone marrow, placenta, prostate, liver,
CC salivary gland, mammary gland, some tumor cell lines, fetal brain,
CC fetal liver, fetal spleen and fetal thymus. No signal at all was
CC detectable in RNA from tissues of the nervous system.
CC {ECO:0000269|PubMed:11738831, ECO:0000269|PubMed:16176263}.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ303380; CAC29064.1; -; mRNA.
DR EMBL; AK093251; BAC04109.1; -; mRNA.
DR EMBL; BC031231; AAH31231.1; -; mRNA.
DR EMBL; AL833011; CAH56302.1; -; mRNA.
DR CCDS; CCDS7789.1; -. [Q9BYT3-1]
DR RefSeq; NP_001275987.1; NM_001289058.1.
DR RefSeq; NP_001275988.1; NM_001289059.1.
DR RefSeq; NP_001275990.1; NM_001289061.1. [Q9BYT3-1]
DR RefSeq; NP_112168.1; NM_030906.3. [Q9BYT3-1]
DR RefSeq; XP_011518590.1; XM_011520288.2.
DR RefSeq; XP_011518592.1; XM_011520290.2. [Q9BYT3-1]
DR RefSeq; XP_011518594.1; XM_011520292.2.
DR RefSeq; XP_011518595.1; XM_011520293.2.
DR RefSeq; XP_011518596.1; XM_011520294.1.
DR RefSeq; XP_011518597.1; XM_011520295.2. [Q9BYT3-1]
DR RefSeq; XP_016873632.1; XM_017018143.1.
DR RefSeq; XP_016873633.1; XM_017018144.1. [Q9BYT3-1]
DR RefSeq; XP_016873634.1; XM_017018145.1. [Q9BYT3-1]
DR RefSeq; XP_016873635.1; XM_017018146.1. [Q9BYT3-1]
DR RefSeq; XP_016873636.1; XM_017018147.1. [Q9BYT3-1]
DR RefSeq; XP_016873637.1; XM_017018148.1. [Q9BYT3-1]
DR RefSeq; XP_016873638.1; XM_017018149.1.
DR RefSeq; XP_016873639.1; XM_017018150.1.
DR RefSeq; XP_016873640.1; XM_017018151.1.
DR RefSeq; XP_016873641.1; XM_017018152.1. [Q9BYT3-1]
DR RefSeq; XP_016873642.1; XM_017018153.1. [Q9BYT3-1]
DR RefSeq; XP_016873643.1; XM_017018154.1. [Q9BYT3-1]
DR RefSeq; XP_016873644.1; XM_017018155.1. [Q9BYT3-1]
DR RefSeq; XP_016873645.1; XM_017018156.1. [Q9BYT3-1]
DR RefSeq; XP_016873648.1; XM_017018159.1. [Q9BYT3-2]
DR RefSeq; XP_016873649.1; XM_017018160.1.
DR AlphaFoldDB; Q9BYT3; -.
DR SMR; Q9BYT3; -.
DR BioGRID; 122426; 15.
DR IntAct; Q9BYT3; 20.
DR STRING; 9606.ENSP00000416750; -.
DR BindingDB; Q9BYT3; -.
DR ChEMBL; CHEMBL6005; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9BYT3; -.
DR GuidetoPHARMACOLOGY; 2221; -.
DR GlyGen; Q9BYT3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BYT3; -.
DR PhosphoSitePlus; Q9BYT3; -.
DR BioMuta; STK33; -.
DR DMDM; 74761329; -.
DR EPD; Q9BYT3; -.
DR jPOST; Q9BYT3; -.
DR MassIVE; Q9BYT3; -.
DR MaxQB; Q9BYT3; -.
DR PaxDb; Q9BYT3; -.
DR PeptideAtlas; Q9BYT3; -.
DR PRIDE; Q9BYT3; -.
DR ProteomicsDB; 79704; -. [Q9BYT3-1]
DR ProteomicsDB; 79705; -. [Q9BYT3-2]
DR Antibodypedia; 11459; 449 antibodies from 35 providers.
DR DNASU; 65975; -.
DR Ensembl; ENST00000315204.5; ENSP00000320754.1; ENSG00000130413.16. [Q9BYT3-1]
DR Ensembl; ENST00000396672.5; ENSP00000379905.1; ENSG00000130413.16. [Q9BYT3-1]
DR Ensembl; ENST00000447869.5; ENSP00000416750.1; ENSG00000130413.16. [Q9BYT3-1]
DR Ensembl; ENST00000687296.1; ENSP00000509322.1; ENSG00000130413.16. [Q9BYT3-1]
DR GeneID; 65975; -.
DR KEGG; hsa:65975; -.
DR MANE-Select; ENST00000687296.1; ENSP00000509322.1; NM_001352389.2; NP_001339318.1.
DR UCSC; uc001mgi.3; human. [Q9BYT3-1]
DR CTD; 65975; -.
DR DisGeNET; 65975; -.
DR GeneCards; STK33; -.
DR HGNC; HGNC:14568; STK33.
DR HPA; ENSG00000130413; Tissue enhanced (testis).
DR MIM; 607670; gene.
DR neXtProt; NX_Q9BYT3; -.
DR OpenTargets; ENSG00000130413; -.
DR PharmGKB; PA37900; -.
DR VEuPathDB; HostDB:ENSG00000130413; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000159050; -.
DR InParanoid; Q9BYT3; -.
DR OMA; CGEPPFM; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q9BYT3; -.
DR TreeFam; TF314166; -.
DR PathwayCommons; Q9BYT3; -.
DR SignaLink; Q9BYT3; -.
DR BioGRID-ORCS; 65975; 10 hits in 1102 CRISPR screens.
DR ChiTaRS; STK33; human.
DR GenomeRNAi; 65975; -.
DR Pharos; Q9BYT3; Tchem.
DR PRO; PR:Q9BYT3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BYT3; protein.
DR Bgee; ENSG00000130413; Expressed in right uterine tube and 112 other tissues.
DR ExpressionAtlas; Q9BYT3; baseline and differential.
DR Genevisible; Q9BYT3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0044773; P:mitotic DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
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 Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..514
FT /note="Serine/threonine-protein kinase 33"
FT /id="PRO_0000232644"
FT DOMAIN 116..381
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 65..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 65..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..423
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..468
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..503
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 238
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 122..130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 145
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q924X7"
FT VAR_SEQ 383..448
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017939"
FT VARIANT 60
FT /note="K -> E (in dbSNP:rs60786172)"
FT /id="VAR_061746"
FT VARIANT 98
FT /note="E -> D (in dbSNP:rs34525052)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041172"
FT VARIANT 160
FT /note="L -> V (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041173"
FT VARIANT 436
FT /note="D -> E (in dbSNP:rs3751096)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041174"
FT VARIANT 437
FT /note="A -> T (in dbSNP:rs3751095)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041175"
FT VARIANT 458
FT /note="A -> E (in dbSNP:rs35296353)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041176"
FT CONFLICT 436..437
FT /note="DA -> ET (in Ref. 3; AAH31231)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="A -> T (in Ref. 3; AAH31231)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 57831 MW; C251691ECB2DAC1A CRC64;
MADSGLDKKS TKCPDCSSAS QKDVLCVCSS KTRVPPVLVV EMSQTSSIGS AESLISLERK
KEKNINRDIT SRKDLPSRTS NVERKASQQQ WGRGNFTEGK VPHIRIENGA AIEEIYTFGR
ILGKGSFGIV IEATDKETET KWAIKKVNKE KAGSSAVKLL EREVNILKSV KHEHIIHLEQ
VFETPKKMYL VMELCEDGEL KEILDRKGHF SENETRWIIQ SLASAIAYLH NNDIVHRDLK
LENIMVKSSL IDDNNEINLN IKVTDFGLAV KKQSRSEAML QATCGTPIYM APEVISAHDY
SQQCDIWSIG VVMYMLLRGE PPFLASSEEK LFELIRKGEL HFENAVWNSI SDCAKSVLKQ
LMKVDPAHRI TAKELLDNQW LTGNKLSSVR PTNVLEMMKE WKNNPESVEE NTTEEKNKPS
TEEKLKSYQP WGNVPDANYT SDEEEEKQST AYEKQFPATS KDNFDMCSSS FTSSKLLPAE
IKGEMEKTPV TPSQGTATKY PAKSGALSRT KKKL
