TSSK6_HUMAN
ID TSSK6_HUMAN Reviewed; 273 AA.
AC Q9BXA6; B2R9F8; Q6ZMC4; Q96LJ4;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Testis-specific serine/threonine-protein kinase 6;
DE Short=TSK-6;
DE Short=TSSK-6;
DE Short=Testis-specific kinase 6;
DE EC=2.7.11.1 {ECO:0000269|PubMed:15870294, ECO:0000269|PubMed:20829357};
DE AltName: Full=Cancer/testis antigen 72;
DE Short=CT72;
DE AltName: Full=Serine/threonine-protein kinase SSTK;
DE AltName: Full=Small serine/threonine kinase;
GN Name=TSSK6 {ECO:0000312|EMBL:AAH14611.1};
GN Synonyms=SSTK {ECO:0000312|EMBL:AAK48827.1}; ORFNames=FKSG82;
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] {ECO:0000305, ECO:0000312|EMBL:AAK48827.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH
RP HSPCB; HSPA8 AND HSPA1A, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-41 AND
RP ASP-135.
RX PubMed=15870294; DOI=10.1128/mcb.25.10.4250-4261.2005;
RA Spiridonov N.A., Wong L., Zerfas P.M., Starost M.F., Pack S.D.,
RA Paweletz C.P., Johnson G.R.;
RT "Identification and characterization of SSTK, a serine/threonine protein
RT kinase essential for male fertility.";
RL Mol. Cell. Biol. 25:4250-4261(2005).
RN [2] {ECO:0000312|EMBL:AAK29414.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang Y.-G., Gong L.;
RT "Identification of FKSG82, a novel gene located on human chromosome 19.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:BAB71697.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ileal mucosa {ECO:0000312|EMBL:BAD18805.1}, and
RC Testis {ECO:0000312|EMBL:BAB71697.1};
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 [4] {ECO:0000312|EMBL:AAK29414.1}
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000312|EMBL:AAH14611.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAH14611.1};
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 CATALYTIC ACTIVITY, INTERACTION WITH TSACC, AND MUTAGENESIS OF LYS-41 AND
RP ASP-135.
RX PubMed=20829357; DOI=10.1074/jbc.m110.134767;
RA Jha K.N., Wong L., Zerfas P.M., De Silva R.S., Fan Y.X., Spiridonov N.A.,
RA Johnson G.R.;
RT "Identification of a novel HSP70-binding cochaperone critical to HSP90-
RT mediated activation of small serine/threonine kinase.";
RL J. Biol. Chem. 285:35180-35187(2010).
CC -!- FUNCTION: Required for sperm production and function. Plays a role in
CC DNA condensation during postmeiotic chromatin remodeling (By
CC similarity). {ECO:0000250|UniProtKB:Q925K9,
CC ECO:0000269|PubMed:15870294}.
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 Evidence={ECO:0000269|PubMed:15870294, ECO:0000269|PubMed:20829357};
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; Evidence={ECO:0000269|PubMed:15870294,
CC ECO:0000269|PubMed:20829357};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15870294};
CC -!- SUBUNIT: Interacts with HSP90; this interaction stabilizes and
CC activates TSSK6 (By similarity). Interacts with the heat shock proteins
CC HSPCB, HSPA8 and HSPA1A. These interactions appear to be required for
CC TSSK6 kinase activity. Interacts with TSACC; this interaction is direct
CC and recruits TSACC to HSP90, which is essential for kinase activity.
CC {ECO:0000250|UniProtKB:Q925K9, ECO:0000269|PubMed:15870294,
CC ECO:0000269|PubMed:20829357}.
CC -!- INTERACTION:
CC Q9BXA6; Q16543: CDC37; NbExp=2; IntAct=EBI-851883, EBI-295634;
CC Q9BXA6; P07900: HSP90AA1; NbExp=2; IntAct=EBI-851883, EBI-296047;
CC Q9BXA6; P08238: HSP90AB1; NbExp=4; IntAct=EBI-851883, EBI-352572;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Expressed at lower
CC levels in colon, small intestine, ovary, prostate, thymus, spleen and
CC peripheral blood leukocytes. {ECO:0000269|PubMed:15870294}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:15870294}.
CC -!- PTM: Ubiquitinated; HSP90 activity negatively regulates ubiquitination
CC and degradation. {ECO:0000250|UniProtKB:Q925K9}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71697.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD18805.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF329483; AAK48827.1; -; mRNA.
DR EMBL; AF348077; AAK29414.1; -; mRNA.
DR EMBL; AK058166; BAB71697.1; ALT_FRAME; mRNA.
DR EMBL; AK172841; BAD18805.1; ALT_FRAME; mRNA.
DR EMBL; AK313767; BAG36505.1; -; mRNA.
DR EMBL; CH471106; EAW84824.1; -; Genomic_DNA.
DR EMBL; BC014611; AAH14611.1; -; mRNA.
DR CCDS; CCDS12403.1; -.
DR RefSeq; NP_114426.1; NM_032037.3.
DR AlphaFoldDB; Q9BXA6; -.
DR SMR; Q9BXA6; -.
DR BioGRID; 123835; 30.
DR IntAct; Q9BXA6; 37.
DR STRING; 9606.ENSP00000466477; -.
DR BindingDB; Q9BXA6; -.
DR ChEMBL; CHEMBL3627582; -.
DR PhosphoSitePlus; Q9BXA6; -.
DR BioMuta; TSSK6; -.
DR DMDM; 74761315; -.
DR MassIVE; Q9BXA6; -.
DR PaxDb; Q9BXA6; -.
DR PeptideAtlas; Q9BXA6; -.
DR PRIDE; Q9BXA6; -.
DR ProteomicsDB; 79391; -.
DR Antibodypedia; 28486; 173 antibodies from 25 providers.
DR DNASU; 83983; -.
DR Ensembl; ENST00000585580.4; ENSP00000466477.1; ENSG00000178093.14.
DR Ensembl; ENST00000587522.3; ENSP00000466056.1; ENSG00000178093.14.
DR GeneID; 83983; -.
DR KEGG; hsa:83983; -.
DR MANE-Select; ENST00000585580.4; ENSP00000466477.1; NM_032037.4; NP_114426.1.
DR UCSC; uc002nmq.4; human.
DR CTD; 83983; -.
DR DisGeNET; 83983; -.
DR GeneCards; TSSK6; -.
DR HGNC; HGNC:30410; TSSK6.
DR HPA; ENSG00000178093; Tissue enriched (testis).
DR MIM; 610712; gene.
DR neXtProt; NX_Q9BXA6; -.
DR OpenTargets; ENSG00000178093; -.
DR PharmGKB; PA142670682; -.
DR VEuPathDB; HostDB:ENSG00000178093; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000160464; -.
DR InParanoid; Q9BXA6; -.
DR OMA; FELIEVC; -.
DR OrthoDB; 947464at2759; -.
DR PhylomeDB; Q9BXA6; -.
DR TreeFam; TF105333; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q9BXA6; -.
DR SignaLink; Q9BXA6; -.
DR BioGRID-ORCS; 83983; 32 hits in 1114 CRISPR screens.
DR ChiTaRS; TSSK6; human.
DR GenomeRNAi; 83983; -.
DR Pharos; Q9BXA6; Tbio.
DR PRO; PR:Q9BXA6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BXA6; protein.
DR Bgee; ENSG00000178093; Expressed in left testis and 99 other tissues.
DR ExpressionAtlas; Q9BXA6; baseline and differential.
DR Genevisible; Q9BXA6; HS.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion 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:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0035092; P:sperm DNA condensation; ISS:UniProtKB.
DR CDD; cd14164; STKc_TSSK6-like; 1.
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 InterPro; IPR042710; TSSK6_STKc.
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 ATP-binding; Developmental protein; Differentiation; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Spermatogenesis; Transferase;
KW Ubl conjugation.
FT CHAIN 1..273
FT /note="Testis-specific serine/threonine-protein kinase 6"
FT /id="PRO_0000227746"
FT DOMAIN 12..267
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027,
FT ECO:0000269|PubMed:15870294"
FT BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9D2E1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:15870294"
FT MUTAGEN 41
FT /note="K->M: Loss of kinase activity. Loss of binding to
FT TSACC."
FT /evidence="ECO:0000269|PubMed:15870294,
FT ECO:0000269|PubMed:20829357"
FT MUTAGEN 135
FT /note="D->N: Loss of kinase activity. No effect of binding
FT to TSACC."
FT /evidence="ECO:0000269|PubMed:15870294,
FT ECO:0000269|PubMed:20829357"
SQ SEQUENCE 273 AA; 30331 MW; 998934C72963C7CE CRC64;
MSGDKLLSEL GYKLGRTIGE GSYSKVKVAT SKKYKGTVAI KVVDRRRAPP DFVNKFLPRE
LSILRGVRHP HIVHVFEFIE VCNGKLYIVM EAAATDLLQA VQRNGRIPGV QARDLFAQIA
GAVRYLHDHH LVHRDLKCEN VLLSPDERRV KLTDFGFGRQ AHGYPDLSTT YCGSAAYASP
EVLLGIPYDP KKYDVWSMGV VLYVMVTGCM PFDDSDIAGL PRRQKRGVLY PEGLELSERC
KALIAELLQF SPSARPSAGQ VARNCWLRAG DSG
