This gene encodes a member of the testis-specific serine/threonine kinase family. The encoded protein is thought to be involved in spermatogenesis via stimulation of the CREB/CRE responsive pathway through phosphorylation of the cAMP responsive element binding protein transcription factor. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 201... See more...

Aliases for TSSK4 Gene

Aliases for TSSK4 Gene

  • Testis Specific Serine Kinase 4 2 3 5
  • Testis-Specific Serine/Threonine-Protein Kinase 4 3 4
  • Serine/Threonine-Protein Kinase 22E 3 4
  • Serine/Threonine Kinase 22E 2 3
  • C14orf20 3 4
  • STK22E 3 4
  • TSK-4 3 4
  • TSSK5 3 4
  • Chromosome 14 Open Reading Frame 20 2
  • Testis-Specific Kinase 4 4
  • EC 2.7.11.1 4
  • EC 2.7.11 50
  • TSSK-4 4
  • TSSK4 5
  • TSK4 3

External Ids for TSSK4 Gene

Previous HGNC Symbols for TSSK4 Gene

  • C14orf20
  • STK22E

Previous GeneCards Identifiers for TSSK4 Gene

  • GC14P023745
  • GC14P024674
  • GC14P004789

Summaries for TSSK4 Gene

Entrez Gene Summary for TSSK4 Gene

  • This gene encodes a member of the testis-specific serine/threonine kinase family. The encoded protein is thought to be involved in spermatogenesis via stimulation of the CREB/CRE responsive pathway through phosphorylation of the cAMP responsive element binding protein transcription factor. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

GeneCards Summary for TSSK4 Gene

TSSK4 (Testis Specific Serine Kinase 4) is a Protein Coding gene. Diseases associated with TSSK4 include Glanders and Oligospermia. Among its related pathways are Sweet Taste Signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is TSSK1B.

UniProtKB/Swiss-Prot Summary for TSSK4 Gene

  • Serine/threonine kinase which is involved in male germ cell development and in mature sperm function (By similarity). May be involved in the Cre/Creb signaling pathway (By similarity). Phosphorylates CREB1 on 'Ser-133' in vitro and can stimulate Cre/Creb pathway in cells (PubMed:15964553). Phosphorylates CREM on 'Ser-116' in vitro (By similarity). Phosphorylates ODF2 on 'Ser-95' (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TSSK4 Gene

Genomics for TSSK4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TSSK4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TSSK4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TSSK4

Top Transcription factor binding sites by QIAGEN in the TSSK4 gene promoter:
  • c-Ets-1
  • deltaCREB
  • GATA-1
  • Lmo2
  • Nkx2-5
  • Nkx5-1
  • PPAR-gamma1
  • PPAR-gamma2
  • RelA
  • RFX1

Genomic Locations for TSSK4 Gene

Latest Assembly
chr14:24,205,524-24,208,362
(GRCh38/hg38)
Size:
2,839 bases
Orientation:
Plus strand

Previous Assembly
chr14:24,674,902-24,677,454
(GRCh37/hg19 by Entrez Gene)
Size:
2,553 bases
Orientation:
Plus strand

chr14:24,674,903-24,677,568
(GRCh37/hg19 by Ensembl)
Size:
2,666 bases
Orientation:
Plus strand

Alternative Locations (GRCh38/hg38)

  • chr14(PATCHES):506,674-509,226 (+)

Genomic View for TSSK4 Gene

Genes around TSSK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TSSK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TSSK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TSSK4 Gene

Proteins for TSSK4 Gene

  • Protein details for TSSK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6SA08-TSSK4_HUMAN
    Recommended name:
    Testis-specific serine/threonine-protein kinase 4
    Protein Accession:
    Q6SA08
    Secondary Accessions:
    • Q2TA60
    • Q6ZNM2

    Protein attributes for TSSK4 Gene

    Size:
    328 amino acids
    Molecular mass:
    37454 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer (By similarity). Interacts with HSP90; this interaction stabilizes and activates TSSK4 (By similarity). Interacts with ODF2 (via C-terminus); this interaction promotes ODF2 phosphorylation on 'Ser-95' (By similarity). May interact with CREM (By similarity). Interacts with CREB1; this interaction facilitates phosphorylation on 'Ser-133' (PubMed:15964553). Interacts with QRICH2 (PubMed:30683861).

    Alternative splice isoforms for TSSK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TSSK4 Gene

Selected DME Specific Peptides for TSSK4 Gene

Q6SA08:
  • RDLKLEN
  • IVHRDLK

Post-translational modifications for TSSK4 Gene

  • Activated by autophosphorylation on Thr-197. ODF2 potentiates the autophosphorylation activity of TSSK4 at Thr-197.
  • Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for TSSK4 Gene

Gene Families for TSSK4 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for TSSK4 Gene

GenScript: Design optimal peptide antigens:
  • Testis-specific serine kinase 4, isoform CRA_c (Q8IZN1_HUMAN)
  • Serine/threonine-protein kinase 22E (TSSK4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6SA08

UniProtKB/Swiss-Prot:

TSSK4_HUMAN :
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Family:
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
genes like me logo Genes that share domains with TSSK4: view

Function for TSSK4 Gene

Molecular function for TSSK4 Gene

UniProtKB/Swiss-Prot Function:
Serine/threonine kinase which is involved in male germ cell development and in mature sperm function (By similarity). May be involved in the Cre/Creb signaling pathway (By similarity). Phosphorylates CREB1 on 'Ser-133' in vitro and can stimulate Cre/Creb pathway in cells (PubMed:15964553). Phosphorylates CREM on 'Ser-116' in vitro (By similarity). Phosphorylates ODF2 on 'Ser-95' (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:15964553};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:15964553};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation on Thr-197.

Enzyme Numbers (IUBMB) for TSSK4 Gene

Phenotypes From GWAS Catalog for TSSK4 Gene

Gene Ontology (GO) - Molecular Function for TSSK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding ISS --
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IBA,ISS --
GO:0005515 protein binding IPI 15964553
genes like me logo Genes that share ontologies with TSSK4: view
genes like me logo Genes that share phenotypes with TSSK4: view

Animal Models for TSSK4 Gene

MGI Knock Outs for TSSK4:

Animal Models for research

  • Taconic Biosciences Mouse Models for TSSK4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TSSK4

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for TSSK4 Gene

Localization for TSSK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TSSK4 Gene

Cytoplasmic vesicle, secretory vesicle, acrosome. Cell projection, cilium, flagellum. Note=In spermatozoa, present in the sperm head and in the flagellum. {ECO:0000250 UniProtKB:Q9D411}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TSSK4 gene
Compartment Confidence
nucleus 3
cytosol 2
extracellular 1
cytoskeleton 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TSSK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001669 acrosomal vesicle IEA --
GO:0005634 nucleus IBA 21873635
GO:0005737 cytoplasm IBA 21873635
GO:0005929 cilium IEA --
GO:0031410 cytoplasmic vesicle IEA --
genes like me logo Genes that share ontologies with TSSK4: view

Pathways & Interactions for TSSK4 Gene

PathCards logo

SuperPathways for TSSK4 Gene

SuperPathway Contained pathways
1 Sweet Taste Signaling
.37
genes like me logo Genes that share pathways with TSSK4: view

Pathways by source for TSSK4 Gene

1 Qiagen pathway for TSSK4 Gene
  • Sperm Motility

SIGNOR curated interactions for TSSK4 Gene

Activates:

Gene Ontology (GO) - Biological Process for TSSK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA,ISS --
GO:0007275 multicellular organism development IEA --
GO:0007283 spermatogenesis IEA --
GO:0007286 spermatid development IEA --
GO:0009566 fertilization IEA --
genes like me logo Genes that share ontologies with TSSK4: view

Drugs & Compounds for TSSK4 Gene

(2) Drugs for TSSK4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
ATP Investigational Nutra 0

(1) Additional Compounds for TSSK4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
58-64-0
genes like me logo Genes that share compounds with TSSK4: view

Transcripts for TSSK4 Gene

mRNA/cDNA for TSSK4 Gene

3 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TSSK4

Alternative Splicing Database (ASD) splice patterns (SP) for TSSK4 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b · 3c · 3d ^ 4a · 4b · 4c
SP1: -
SP2: - -
SP3: -
SP4: -
SP5:

Relevant External Links for TSSK4 Gene

GeneLoc Exon Structure for
TSSK4

Expression for TSSK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TSSK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Testis (Reproductive System)

mRNA differential expression in normal tissues according to GTEx for TSSK4 Gene

This gene is overexpressed in Testis (x12.4).

Protein differential expression in normal tissues from HIPED for TSSK4 Gene

This gene is overexpressed in CD8 Tcells (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TSSK4 Gene



Protein tissue co-expression partners for TSSK4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TSSK4

SOURCE GeneReport for Unigene cluster for TSSK4 Gene:

Hs.314432

mRNA Expression by UniProt/SwissProt for TSSK4 Gene:

Q6SA08-TSSK4_HUMAN
Tissue specificity: Expressed only in the testis.
genes like me logo Genes that share expression patterns with TSSK4: view

No data available for Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for TSSK4 Gene

Orthologs for TSSK4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TSSK4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TSSK4 29 30
  • 99.31 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TSSK4 29 30
  • 90.04 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TSSK4 29 30
  • 89.88 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tssk4 29
  • 89.84 (n)
Mouse
(Mus musculus)
Mammalia Tssk4 29 16 30
  • 88.46 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TSSK4 30
  • 79 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TSSK4 30
  • 74 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG9222 29 30
  • 54.06 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008735 29
  • 50.52 (n)
Worm
(Caenorhabditis elegans)
Secernentea W02B12.12 29
  • 45.07 (n)
F23C8.8 30
  • 27 (a)
ManyToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KIN4 30
  • 11 (a)
ManyToMany
FRK1 30
  • 11 (a)
ManyToMany
-- 30
  • 10 (a)
ManyToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 35 (a)
ManyToMany
Species where no ortholog for TSSK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Zebrafish (Danio rerio)

Evolution for TSSK4 Gene

ENSEMBL:
Gene Tree for TSSK4 (if available)
TreeFam:
Gene Tree for TSSK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TSSK4: view image
Alliance of Genome Resources:
Additional Orthologs for TSSK4

Paralogs for TSSK4 Gene

(39) SIMAP similar genes for TSSK4 Gene using alignment to 4 proteins:

  • TSSK4_HUMAN
  • H0YJ36_HUMAN
  • H0YJB1_HUMAN
  • H7C3J1_HUMAN
genes like me logo Genes that share paralogs with TSSK4: view

Variants for TSSK4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TSSK4 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
rs1270764 -- p.Gln196Arg
rs34083933 -- p.Tyr89Cys
rs35244223 -- p.Thr327Met
rs35468205 -- p.Val145Met
rs36036137 -- p.His33Tyr

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TSSK4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for TSSK4 Gene

Residual Variation Intolerance Score: 62.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.22; 69.94% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TSSK4 Gene

Human Gene Mutation Database (HGMD)
TSSK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TSSK4
Leiden Open Variation Database (LOVD)
TSSK4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for TSSK4 Gene

Disorders for TSSK4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for TSSK4 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
glanders
  • farcy pipes
oligospermia
male infertility
  • infertility male
- elite association - COSMIC cancer census association via MalaCards
Search TSSK4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TSSK4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TSSK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TSSK4 Gene

Publications for TSSK4 Gene

  1. Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella. (PMID: 30683861) Shen Y … Xu W (Nature communications 2019) 3 4
  2. Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent. (PMID: 20378615) Aston KI … Carrell DT (Human reproduction (Oxford, England) 2010) 3 40
  3. Mutation screening and association study of the TSSK4 Gene in Chinese infertile men with impaired spermatogenesis. (PMID: 18390560) Su D … Zhang S (Journal of andrology 2008) 3 40
  4. TSSK5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates CREB at Ser-133, and stimulates the CRE/CREB responsive pathway. (PMID: 15964553) Chen X … Yu L (Biochemical and biophysical research communications 2005) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for TSSK4 Gene

Sources for TSSK4 Gene