TSSK1_MOUSE
ID TSSK1_MOUSE Reviewed; 365 AA.
AC Q61241; Q80YU1;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Testis-specific serine/threonine-protein kinase 1;
DE Short=TSK-1;
DE Short=TSK1;
DE Short=TSSK-1;
DE Short=Testis-specific kinase 1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:23599433};
DE AltName: Full=Serine/threonine-protein kinase 22A;
GN Name=Tssk1b; Synonyms=Stk22a, Tssk1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8112611; DOI=10.1016/0378-1119(94)90762-5;
RA Bielke W., Blaschke R.J., Miescher G.C., Zurcher G., Andres A.-C.,
RA Ziemiecki A.;
RT "Characterization of a novel murine testis-specific serine/threonine
RT kinase.";
RL Gene 139:235-239(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9651519; DOI=10.1016/s0925-4773(98)00060-4;
RA Nayak S., Galili N., Buck C.A.;
RT "Immunohistochemical analysis of the expression of two serine-threonine
RT kinases in the maturing mouse testis.";
RL Mech. Dev. 74:171-174(1998).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9412477; DOI=10.1083/jcb.139.7.1851;
RA Kueng P., Nikolova Z., Djonov V., Hemphill A., Rohrbach V., Boehlen D.,
RA Zuercher G., Andres A.-C., Ziemiecki A.;
RT "A novel family of serine/threonine kinases participating in
RT spermiogenesis.";
RL J. Cell Biol. 139:1851-1859(1997).
RN [6]
RP INTERACTION WITH TSSK2.
RX PubMed=10781952; DOI=10.1016/s0925-4773(00)00255-0;
RA Zuercher G., Rohrbach V., Andres A.-C., Ziemiecki A.;
RT "A novel member of the testis specific serine kinase family, tssk-3,
RT expressed in the Leydig cells of sexually mature mice.";
RL Mech. Dev. 93:175-177(2000).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=18533145; DOI=10.1016/j.ydbio.2008.03.047;
RA Xu B., Hao Z., Jha K.N., Zhang Z., Urekar C., Digilio L., Pulido S.,
RA Strauss J.F. III, Flickinger C.J., Herr J.C.;
RT "Targeted deletion of Tssk1 and 2 causes male infertility due to
RT haploinsufficiency.";
RL Dev. Biol. 319:211-222(2008).
RN [8]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20053632; DOI=10.1242/jcs.059949;
RA Shang P., Baarends W.M., Hoogerbrugge J., Ooms M.P., van Cappellen W.A.,
RA de Jong A.A., Dohle G.R., van Eenennaam H., Gossen J.A., Grootegoed J.A.;
RT "Functional transformation of the chromatoid body in mouse spermatids
RT requires testis-specific serine/threonine kinases.";
RL J. Cell Sci. 123:331-339(2010).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20729278; DOI=10.1093/molehr/gaq071;
RA Li Y., Sosnik J., Brassard L., Reese M., Spiridonov N.A., Bates T.C.,
RA Johnson G.R., Anguita J., Visconti P.E., Salicioni A.M.;
RT "Expression and localization of five members of the testis-specific serine
RT kinase (Tssk) family in mouse and human sperm and testis.";
RL Mol. Hum. Reprod. 17:42-56(2011).
RN [10] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH HSP90, AND
RP UBIQUITINATION.
RX PubMed=23599433; DOI=10.1074/jbc.m112.400978;
RA Jha K.N., Coleman A.R., Wong L., Salicioni A.M., Howcroft E., Johnson G.R.;
RT "Heat shock protein 90 functions to stabilize and activate the testis-
RT specific serine/threonine kinases, a family of kinases essential for male
RT fertility.";
RL J. Biol. Chem. 288:16308-16320(2013).
CC -!- FUNCTION: Testis-specific serine/threonine-protein kinase required
CC during spermatid development (PubMed:20053632, PubMed:23599433).
CC Phosphorylates 'Ser-281' of TSKS (PubMed:20053632). Involved in the
CC late stages of spermatogenesis, during the reconstruction of the
CC cytoplasm (PubMed:20053632). During spermatogenesis, required for the
CC transformation of a ring-shaped structure around the base of the
CC flagellum originating from the chromatoid body (PubMed:20053632).
CC {ECO:0000269|PubMed:20053632, ECO:0000269|PubMed:23599433}.
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:23599433};
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:23599433};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:23599433};
CC Note=Mg(2+) and Mn(2+) were both present in the kinase buffer but
CC Mg(2+) is likely to be the in vivo cofactor.
CC {ECO:0000305|PubMed:23599433};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-174,
CC potentially by autophosphorylation. {ECO:0000250|UniProtKB:Q9BXA7}.
CC -!- SUBUNIT: Interacts with TSSK2 (PubMed:10781952). Interacts with HSP90;
CC this interaction stabilizes TSSK1 (PubMed:23599433).
CC {ECO:0000269|PubMed:10781952, ECO:0000269|PubMed:23599433}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasmic vesicle, secretory
CC vesicle, acrosome. Cell projection, cilium, flagellum. Note=In
CC spermatozoa, present in the sperm head and in the flagellum.
CC -!- TISSUE SPECIFICITY: Testis-specific. Expressed only in postmeiotic
CC spermatids at the final stages of cytodifferentiation in the
CC seminiferous tubules (at protein level). Not detected in released
CC sperms in the lumen of the seminiferous tubules and the epididymis.
CC {ECO:0000269|PubMed:20729278, ECO:0000269|PubMed:9412477,
CC ECO:0000269|PubMed:9651519}.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:Q9BXA7}.
CC -!- PTM: Ubiquitinated; HSP90 activity negatively regulates ubiquitination
CC and degradation. {ECO:0000269|PubMed:23599433}.
CC -!- DISRUPTION PHENOTYPE: Male mice lacking Tssk1b and Tssk2 are sterile
CC due to haploinsufficiency. chimeras show failure to form elongated
CC spermatids, apoptosis of spermatocytes and spermatids, and the
CC appearance of numerous round cells in the epididymal lumen. Elongating
CC spermatids possess a collapsed mitochondrial sheath.
CC {ECO:0000269|PubMed:18533145, ECO:0000269|PubMed:20053632}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; U01840; AAA99535.1; -; mRNA.
DR EMBL; CH466521; EDK97490.1; -; Genomic_DNA.
DR EMBL; BC050772; AAH50772.2; -; mRNA.
DR CCDS; CCDS28011.1; -.
DR RefSeq; NP_033461.2; NM_009435.2.
DR AlphaFoldDB; Q61241; -.
DR SMR; Q61241; -.
DR STRING; 10090.ENSMUSP00000040302; -.
DR BindingDB; Q61241; -.
DR ChEMBL; CHEMBL3804750; -.
DR iPTMnet; Q61241; -.
DR PhosphoSitePlus; Q61241; -.
DR REPRODUCTION-2DPAGE; IPI00403935; -.
DR PaxDb; Q61241; -.
DR PRIDE; Q61241; -.
DR ProteomicsDB; 300142; -.
DR Antibodypedia; 25396; 47 antibodies from 18 providers.
DR DNASU; 22114; -.
DR Ensembl; ENSMUST00000046937; ENSMUSP00000040302; ENSMUSG00000041566.
DR GeneID; 22114; -.
DR KEGG; mmu:22114; -.
DR UCSC; uc007ymk.1; mouse.
DR CTD; 22114; -.
DR MGI; MGI:1347557; Tssk1.
DR VEuPathDB; HostDB:ENSMUSG00000041566; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000163130; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q61241; -.
DR OMA; EYITDSC; -.
DR OrthoDB; 947464at2759; -.
DR PhylomeDB; Q61241; -.
DR TreeFam; TF352374; -.
DR BioGRID-ORCS; 22114; 0 hits in 74 CRISPR screens.
DR PRO; PR:Q61241; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q61241; protein.
DR Bgee; ENSMUSG00000041566; Expressed in seminiferous tubule of testis and 9 other tissues.
DR Genevisible; Q61241; MM.
DR GO; GO:0001669; C:acrosomal vesicle; TAS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS: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; IPI:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; TAS: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 ATP-binding; Cell projection; Cilium; Cytoplasm; Cytoplasmic vesicle;
KW Developmental protein; Differentiation; Flagellum; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Spermatogenesis; Transferase;
KW Ubl conjugation.
FT CHAIN 1..365
FT /note="Testis-specific serine/threonine-protein kinase 1"
FT /id="PRO_0000086767"
FT DOMAIN 12..272
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 282..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..330
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..346
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..365
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="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 MOD_RES 174
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXA7"
FT CONFLICT 80
FT /note="E -> A (in Ref. 1; AAA99535)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="C -> S (in Ref. 1; AAA99535)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="Missing (in Ref. 1; AAA99535)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 365 AA; 41589 MW; 06CF52ABD9616A37 CRC64;
MDDAAVLKRR GYIMGINLGE GSYAKVKSAY SERLKFNVAV KIIDRKKAPS DFLEKFLPRE
IEILAMLNHR SIVKTYEIFE TSDGKVYIVM ELGVQGDLLE FIKTRGALQE DDARKKFHQL
SSAIKYCHDL DVVHRDLKCE NLLLDKDFNI KLSDFGFSKR CLRDDSGRLI LSKTFCGSAA
YAAPEVLQGI PYQPKVYDIW SLGVILYIMV CGSMPYDDSN IKKMLRIQKE HRVNFPRSKH
LTGECKDLIY RMLQPDVNRR LHIDEILNHC WVQPKARGLS SGAINKEGES SRATEPSWIP
EPGADKKSAT KLEPREEARS EARSESKPQE DTLQVVRQSE NVGLSSELNR DTEEGHPQQP
SETHT
