TSSK4_HUMAN
ID TSSK4_HUMAN Reviewed; 328 AA.
AC Q6SA08; Q2TA60; Q6ZNM2;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Testis-specific serine/threonine-protein kinase 4 {ECO:0000312|HGNC:HGNC:19825};
DE Short=TSK-4 {ECO:0000305};
DE Short=TSSK-4 {ECO:0000312|HGNC:HGNC:19825};
DE Short=Testis-specific kinase 4 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:15964553};
DE AltName: Full=Serine/threonine-protein kinase 22E {ECO:0000312|HGNC:HGNC:19825};
GN Name=TSSK4 {ECO:0000312|HGNC:HGNC:19825};
GN Synonyms=C14orf20 {ECO:0000312|HGNC:HGNC:19825},
GN STK22E {ECO:0000312|HGNC:HGNC:19825}, TSSK5 {ECO:0000303|PubMed:15964553};
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), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, INTERACTION WITH CREB1, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP LYS-54.
RC TISSUE=Testis;
RX PubMed=15964553; DOI=10.1016/j.bbrc.2005.05.157;
RA Chen X., Lin G., Wei Y., Hexige S., Niu Y., Liu L., Yang C., Yu L.;
RT "TSSK5, a novel member of the testis-specific serine/threonine kinase
RT family, phosphorylates CREB at Ser-133, and stimulates the CRE/CREB
RT responsive pathway.";
RL Biochem. Biophys. Res. Commun. 333:742-749(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 3).
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 INTERACTION WITH QRICH2.
RX PubMed=30683861; DOI=10.1038/s41467-018-08182-x;
RA Shen Y., Zhang F., Li F., Jiang X., Yang Y., Li X., Li W., Wang X.,
RA Cheng J., Liu M., Zhang X., Yuan G., Pei X., Cai K., Hu F., Sun J., Yan L.,
RA Tang L., Jiang C., Tu W., Xu J., Wu H., Kong W., Li S., Wang K., Sheng K.,
RA Zhao X., Yue H., Yang X., Xu W.;
RT "Loss-of-function mutations in QRICH2 cause male infertility with multiple
RT morphological abnormalities of the sperm flagella.";
RL Nat. Commun. 10:433-433(2019).
RN [5]
RP VARIANTS [LARGE SCALE ANALYSIS] TYR-33; CYS-89; MET-145; ARG-196 AND
RP MET-327.
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 kinase which is involved in male germ cell
CC development and in mature sperm function (By similarity). May be
CC involved in the Cre/Creb signaling pathway (By similarity).
CC Phosphorylates CREB1 on 'Ser-133' in vitro and can stimulate Cre/Creb
CC pathway in cells (PubMed:15964553). Phosphorylates CREM on 'Ser-116' in
CC vitro (By similarity). Phosphorylates ODF2 on 'Ser-95' (By similarity).
CC {ECO:0000250|UniProtKB:Q9D411, ECO:0000269|PubMed:15964553}.
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:15964553};
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:15964553};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15964553};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-197.
CC {ECO:0000250|UniProtKB:Q9D411}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with HSP90; this
CC interaction stabilizes and activates TSSK4 (By similarity). Interacts
CC with ODF2 (via C-terminus); this interaction promotes ODF2
CC phosphorylation on 'Ser-95' (By similarity). May interact with CREM (By
CC similarity). Interacts with CREB1; this interaction facilitates
CC phosphorylation on 'Ser-133' (PubMed:15964553). Interacts with QRICH2
CC (PubMed:30683861). {ECO:0000250|UniProtKB:Q9D411,
CC ECO:0000269|PubMed:15964553, ECO:0000269|PubMed:30683861}.
CC -!- INTERACTION:
CC Q6SA08; P16220: CREB1; NbExp=5; IntAct=EBI-1202583, EBI-711855;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000250|UniProtKB:Q9D411}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:Q9D411}. Note=In spermatozoa, present in the
CC sperm head and in the flagellum. {ECO:0000250|UniProtKB:Q9D411}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6SA08-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6SA08-2; Sequence=VSP_023560;
CC Name=3;
CC IsoId=Q6SA08-3; Sequence=VSP_023559;
CC -!- TISSUE SPECIFICITY: Expressed only in the testis.
CC {ECO:0000269|PubMed:15964553}.
CC -!- PTM: Activated by autophosphorylation on Thr-197. ODF2 potentiates the
CC autophosphorylation activity of TSSK4 at Thr-197.
CC {ECO:0000250|UniProtKB:Q9D411}.
CC -!- PTM: Ubiquitinated; HSP90 activity negatively regulates ubiquitination
CC and degradation. {ECO:0000250|UniProtKB:Q9D411}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {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; AY461663; AAS17971.1; -; mRNA.
DR EMBL; AK131042; BAC85482.1; -; mRNA.
DR EMBL; BC111088; AAI11089.1; -; mRNA.
DR CCDS; CCDS53890.1; -. [Q6SA08-2]
DR CCDS; CCDS76662.1; -. [Q6SA08-3]
DR CCDS; CCDS9618.1; -. [Q6SA08-1]
DR RefSeq; NP_001171668.1; NM_001184739.1. [Q6SA08-2]
DR RefSeq; NP_001294996.1; NM_001308067.1. [Q6SA08-3]
DR RefSeq; NP_777604.2; NM_174944.3. [Q6SA08-1]
DR AlphaFoldDB; Q6SA08; -.
DR SMR; Q6SA08; -.
DR BioGRID; 129625; 8.
DR IntAct; Q6SA08; 1.
DR STRING; 9606.ENSP00000339179; -.
DR BindingDB; Q6SA08; -.
DR ChEMBL; CHEMBL4295868; -.
DR iPTMnet; Q6SA08; -.
DR PhosphoSitePlus; Q6SA08; -.
DR BioMuta; TSSK4; -.
DR DMDM; 62287888; -.
DR EPD; Q6SA08; -.
DR MassIVE; Q6SA08; -.
DR PaxDb; Q6SA08; -.
DR PeptideAtlas; Q6SA08; -.
DR PRIDE; Q6SA08; -.
DR ProteomicsDB; 67353; -. [Q6SA08-1]
DR ProteomicsDB; 67354; -. [Q6SA08-2]
DR ProteomicsDB; 67355; -. [Q6SA08-3]
DR Antibodypedia; 22738; 141 antibodies from 22 providers.
DR DNASU; 283629; -.
DR Ensembl; ENST00000287913.10; ENSP00000287913.6; ENSG00000139908.15. [Q6SA08-1]
DR Ensembl; ENST00000339917.10; ENSP00000339179.5; ENSG00000139908.15. [Q6SA08-2]
DR Ensembl; ENST00000556621.5; ENSP00000452054.1; ENSG00000139908.15. [Q6SA08-3]
DR Ensembl; ENST00000643387.1; ENSP00000495573.1; ENSG00000285140.2. [Q6SA08-1]
DR Ensembl; ENST00000645264.1; ENSP00000496404.1; ENSG00000285140.2. [Q6SA08-3]
DR Ensembl; ENST00000645272.2; ENSP00000496710.1; ENSG00000285140.2. [Q6SA08-2]
DR GeneID; 283629; -.
DR KEGG; hsa:283629; -.
DR MANE-Select; ENST00000339917.10; ENSP00000339179.5; NM_001184739.2; NP_001171668.1. [Q6SA08-2]
DR UCSC; uc001wne.4; human. [Q6SA08-1]
DR CTD; 283629; -.
DR DisGeNET; 283629; -.
DR GeneCards; TSSK4; -.
DR HGNC; HGNC:19825; TSSK4.
DR HPA; ENSG00000139908; Tissue enriched (testis).
DR MIM; 610711; gene.
DR neXtProt; NX_Q6SA08; -.
DR OpenTargets; ENSG00000139908; -.
DR PharmGKB; PA134908318; -.
DR VEuPathDB; HostDB:ENSG00000139908; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000161286; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q6SA08; -.
DR OMA; YMILELA; -.
DR OrthoDB; 947464at2759; -.
DR PhylomeDB; Q6SA08; -.
DR TreeFam; TF105333; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q6SA08; -.
DR SignaLink; Q6SA08; -.
DR SIGNOR; Q6SA08; -.
DR BioGRID-ORCS; 283629; 47 hits in 1106 CRISPR screens.
DR ChiTaRS; TSSK4; human.
DR GenomeRNAi; 283629; -.
DR Pharos; Q6SA08; Tbio.
DR PRO; PR:Q6SA08; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q6SA08; protein.
DR Bgee; ENSG00000139908; Expressed in left testis and 104 other tissues.
DR ExpressionAtlas; Q6SA08; baseline and differential.
DR Genevisible; Q6SA08; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0036126; C:sperm flagellum; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
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:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0030317; P:flagellated sperm motility; 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:1990443; P:peptidyl-threonine autophosphorylation; IEA:Ensembl.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
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; Cell projection; Cilium;
KW Cytoplasmic vesicle; Developmental protein; Differentiation; Flagellum;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Spermatogenesis;
KW Transferase; Ubl conjugation.
FT CHAIN 1..328
FT /note="Testis-specific serine/threonine-protein kinase 4"
FT /id="PRO_0000086772"
FT DOMAIN 25..293
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 148
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 31..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305|PubMed:15964553"
FT MOD_RES 197
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9D411"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023559"
FT VAR_SEQ 147
FT /note="R -> RLMPSLSAAGR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023560"
FT VARIANT 33
FT /note="H -> Y (in dbSNP:rs36036137)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041247"
FT VARIANT 89
FT /note="Y -> C (in dbSNP:rs34083933)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041248"
FT VARIANT 145
FT /note="V -> M (in dbSNP:rs35468205)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041249"
FT VARIANT 196
FT /note="Q -> R (in dbSNP:rs1270764)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041250"
FT VARIANT 327
FT /note="T -> M (in dbSNP:rs35244223)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041251"
FT MUTAGEN 54
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15964553"
FT CONFLICT 115
FT /note="Q -> R (in Ref. 2; BAC85482)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 328 AA; 37454 MW; C78502FF6F71754C CRC64;
MGKGDVLEAA PTTTAYHSLM DEYGYEVGKA IGHGSYGSVY EAFYTKQKVM VAVKIISKKK
ASDDYLNKFL PREIQVMKVL RHKYLINFYR AIESTSRVYI ILELAQGGDV LEWIQRYGAC
SEPLAGKWFS QLTLGIAYLH SKSIVHRDLK LENLLLDKWE NVKISDFGFA KMVPSNQPVG
CSPSYRQVNC FSHLSQTYCG SFAYACPEIL RGLPYNPFLS DTWSMGVILY TLVVAHLPFD
DTNLKKLLRE TQKEVTFPAN HTISQECKNL ILQMLRQATK RATILDIIKD SWVLKFQPEQ
PTHEIRLLEA MCQLHNTTKQ HQSLQITT
