TSSK2_MOUSE
ID TSSK2_MOUSE Reviewed; 358 AA.
AC O54863; Q6P8M9;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Testis-specific serine/threonine-protein kinase 2;
DE Short=TSK-2;
DE Short=TSK2;
DE Short=TSSK-2;
DE Short=Testis-specific kinase 2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:23599433};
DE AltName: Full=Serine/threonine-protein kinase 22B;
GN Name=Tssk2; Synonyms=Stk22b;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
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 [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 INTERACTION WITH TSSK1B.
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SPAG16.
RX PubMed=18367677; DOI=10.1095/biolreprod.107.066308;
RA Zhang Z., Shen X., Jones B.H., Xu B., Herr J.C., Strauss J.F. III;
RT "Phosphorylation of mouse sperm axoneme central apparatus protein SPAG16L
RT by a testis-specific kinase, TSSK2.";
RL Biol. Reprod. 79:75-83(2008).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=18495105; DOI=10.1016/j.ydbio.2008.03.043;
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 "TSKS concentrates in spermatid centrioles during flagellogenesis.";
RL Dev. Biol. 319:201-210(2008).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND 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 [9]
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 [10]
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 [11] {ECO:0000305}
RP CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH HSP90, AND 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. Phosphorylates 'Ser-281' of TSKS and
CC SPAG16. Involved in the late stages of spermatogenesis, during the
CC reconstruction of the cytoplasm. During spermatogenesis, required for
CC the transformation of a ring-shaped structure around the base of the
CC flagellum originating from the chromatoid body.
CC {ECO:0000269|PubMed:18367677, ECO:0000269|PubMed:18533145,
CC ECO:0000269|PubMed:20053632, ECO:0000269|PubMed:9412477}.
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}.
CC -!- SUBUNIT: Interacts with TSSK1B (PubMed:10781952, PubMed:18367677).
CC Interacts with HSP90; this interaction stabilizes TSSK2
CC (PubMed:23599433). {ECO:0000269|PubMed:10781952,
CC ECO:0000269|PubMed:18367677, ECO:0000269|PubMed:23599433}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole. Cytoplasmic vesicle,
CC secretory vesicle, acrosome. Note=Present in the cytoplasm of
CC elongating spermatids. In spermatozoa, localizes in the equatorial
CC segment, neck, the midpiece and in a specific sperm head compartment.
CC In spermatids, concentrates in centrioles during flagellogenesis.
CC Localizes in the tail and acrosomal regions of epididymal sperm.
CC -!- TISSUE SPECIFICITY: Testis-specific. Expressed only in the spermatids
CC postmeiotically 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. Also present in the
CC epididymal sperm (at protein level). {ECO:0000269|PubMed:18533145,
CC ECO:0000269|PubMed:20729278, ECO:0000269|PubMed:9412477,
CC ECO:0000269|PubMed:9651519}.
CC -!- DEVELOPMENTAL STAGE: First expression detected at 3.5 to 4 weeks.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:Q96PF2}.
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; AF019926; AAC03367.1; -; mRNA.
DR EMBL; BC061175; AAH61175.1; -; mRNA.
DR EMBL; CH466521; EDK97491.1; -; Genomic_DNA.
DR CCDS; CCDS28012.1; -.
DR RefSeq; NP_033462.2; NM_009436.2.
DR AlphaFoldDB; O54863; -.
DR SMR; O54863; -.
DR IntAct; O54863; 1.
DR MINT; O54863; -.
DR STRING; 10090.ENSMUSP00000051035; -.
DR iPTMnet; O54863; -.
DR PhosphoSitePlus; O54863; -.
DR PaxDb; O54863; -.
DR PRIDE; O54863; -.
DR ProteomicsDB; 298001; -.
DR Antibodypedia; 22857; 71 antibodies from 15 providers.
DR DNASU; 22115; -.
DR Ensembl; ENSMUST00000055374; ENSMUSP00000051035; ENSMUSG00000045521.
DR GeneID; 22115; -.
DR KEGG; mmu:22115; -.
DR UCSC; uc007yml.1; mouse.
DR CTD; 23617; -.
DR MGI; MGI:1347559; Tssk2.
DR VEuPathDB; HostDB:ENSMUSG00000045521; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000162226; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; O54863; -.
DR OMA; WMQPPKP; -.
DR OrthoDB; 947464at2759; -.
DR PhylomeDB; O54863; -.
DR TreeFam; TF352374; -.
DR BioGRID-ORCS; 22115; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Tssk2; mouse.
DR PRO; PR:O54863; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; O54863; protein.
DR Bgee; ENSMUSG00000045521; Expressed in spermatid and 12 other tissues.
DR Genevisible; O54863; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0005814; C:centriole; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; 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:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; IMP: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; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Developmental protein; Differentiation; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Spermatogenesis; Transferase;
KW Ubl conjugation.
FT CHAIN 1..358
FT /note="Testis-specific serine/threonine-protein kinase 2"
FT /id="PRO_0000086769"
FT DOMAIN 12..272
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 296..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..317
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..358
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 CONFLICT 100
FT /note="E -> T (in Ref. 1; AAC03367)"
FT /evidence="ECO:0000305"
FT CONFLICT 113..114
FT /note="AR -> GG (in Ref. 1; AAC03367)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="L -> V (in Ref. 1; AAC03367)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="R -> G (in Ref. 1; AAC03367)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="L -> R (in Ref. 1; AAC03367)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="Missing (in Ref. 1; AAC03367)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 358 AA; 41022 MW; 551F2AAEB0BBAF31 CRC64;
MDDAAVLRKK GYIVGINLGK GSYAKVKSAY SERLKFNVAV KIIDRKKTPT DFVERFLPRE
MDILATVNHR SIIKTYEIFE TSDGRIYIVM ELGVQGDLLE FIKCRGALHE DVARKMFRQL
SSAVKYCHDL DVVHRDLKCE NLLLDKDFNI KLSDFGFSKR CLRDGSGRIV LSKTFCGSAA
YAAPEVLQGI PYQPKVYDIW SLGVILYIMV CGSMPYDDSD IKKMLRIQKE HRVDFPRSKN
LTGECKDLIY RILQPDVNRR LHIDEILSHS WLQPPKPKAM SSASFKREGE GKYRADCKLD
TRPGSRPEHR PDHKLATKPQ QRMLVTPENE DRMEDRLAET SRAKDHHISG AEVEKAST
