RBCC

Full text data of STK10

STK10 (LOK) [Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein kinase 10; 2.7.11.1 (Lymphocyte-oriented kinase)

UniProt O94804
ID STK10_HUMAN Reviewed; 968 AA.
AC O94804; A6ND35; B2R8F5; B3KMY1; Q6NSK0; Q9UIW4;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Serine/threonine-protein kinase 10;
DE EC=2.7.11.1;
DE AltName: Full=Lymphocyte-oriented kinase;
GN Name=STK10; Synonyms=LOK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10199912; DOI=10.1007/s002510050509;
RA Kuramochi S., Matsuda Y., Okamoto M., Kitamura F., Yonekawa H.,
RA Karasuyama H.;
RT "Molecular cloning of the human gene STK10 encoding lymphocyte-
RT oriented kinase, and comparative chromosomal mapping of the human,
RT mouse, and rat homologues.";
RL Immunogenetics 49:369-375(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma, and 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 814-968.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP FUNCTION.
RX PubMed=11903060; DOI=10.1042/0264-6021:3630175;
RA Tao L., Wadsworth S., Mercer J., Mueller C., Lynn K., Siekierka J.,
RA August A.;
RT "Opposing roles of serine/threonine kinases MEKK1 and LOK in
RT regulating the CD28 responsive element in T-cells.";
RL Biochem. J. 363:175-182(2002).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-65.
RX PubMed=12639966; DOI=10.1074/jbc.M212556200;
RA Walter S.A., Cutler R.E. Jr., Martinez R., Gishizky M., Hill R.J.;
RT "Stk10, a new member of the polo-like kinase kinase family highly
RT expressed in hematopoietic tissue.";
RL J. Biol. Chem. 278:18221-18228(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185; SER-191 AND
RP SER-438, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-191; SER-454 AND
RP THR-952, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185; SER-191; SER-438;
RP SER-444 AND SER-549, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19255442; DOI=10.1073/pnas.0805963106;
RA Belkina N.V., Liu Y., Hao J.J., Karasuyama H., Shaw S.;
RT "LOK is a major ERM kinase in resting lymphocytes and regulates
RT cytoskeletal rearrangement through ERM phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4707-4712(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP ENZYME REGULATION.
RX PubMed=21606217; DOI=10.1124/mol.110.070862;
RA Yamamoto N., Honma M., Suzuki H.;
RT "Off-target serine/threonine kinase 10 inhibition by erlotinib
RT enhances lymphocytic activity leading to severe skin disorders.";
RL Mol. Pharmacol. 80:466-475(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 18-317 IN COMPLEX WITH
RP PYRROLE-INDOLINONE INHIBITOR, ENZYME REGULATION, AUTOPHOSPHORYLATION,
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=18239682; DOI=10.1038/emboj.2008.8;
RA Pike A.C., Rellos P., Niesen F.H., Turnbull A., Oliver A.W.,
RA Parker S.A., Turk B.E., Pearl L.H., Knapp S.;
RT "Activation segment dimerization: a mechanism for kinase
RT autophosphorylation of non-consensus sites.";
RL EMBO J. 27:704-714(2008).
RN [23]
RP VARIANT TGCT GLU-277.
RX PubMed=16175573; DOI=10.1002/gcc.20265;
RA Bignell G., Smith R., Hunter C., Stephens P., Davies H., Greenman C.,
RA Teague J., Butler A., Edkins S., Stevens C., O'meara S., Parker A.,
RA Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J.,
RA Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K.,
RA Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R.,
RA Lugg R., Menzies A., Perry J., Petty R., Raine K., Shepherd R.,
RA Small A., Solomon H., Stephens Y., Tofts C., Varian J., Webb A.,
RA West S., Widaa S., Yates A., Gillis A.J.M., Stoop H.J.,
RA van Gurp R.J.H.L.M., Oosterhuis J.W., Looijenga L.H.J., Futreal P.A.,
RA Wooster R., Stratton M.R.;
RT "Sequence analysis of the protein kinase gene family in human
RT testicular germ-cell tumors of adolescents and adults.";
RL Genes Chromosomes Cancer 45:42-46(2006).
RN [24]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-268; GLU-277; TRP-322; ILE-336;
RP SER-467; THR-710; LEU-853; THR-905 AND TYR-947.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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-protein kinase involved in regulation
CC of lymphocyte migration. Phosphorylates MSN, and possibly PLK1.
CC Involved in regulation of lymphocyte migration by mediating
CC phosphorylation of ERM proteins such as MSN. Acts as a negative
CC regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator
CC by acting as a polo kinase kinase: mediates phosphorylation of
CC PLK1 in vitro; however such data require additional evidences in
CC vivo.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Inhibited by the pyrrole-indolinone inhibitor
CC SU11274 (K00593): intercalates between the ATP-binding Lys-65 and
CC alpha-C glutamate (Glu-81), resulting in a partial disordering of
CC the lysine side chain. Also specifically inhibited by erlotinib.
CC Slightly inhibited by gefitinib.
CC -!- SUBUNIT: Homodimer; homodimerization is required for activation
CC segment autophosphorylation.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-3951541, EBI-3951541;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in rapidly proliferating
CC tissues (spleen, placenta, and peripheral blood leukocytes). Also
CC expressed in brain, heart, skeletal muscle, colon, thymus, kidney,
CC liver, small intestine and lung.
CC -!- PTM: Autophosphorylates following homodimerization, leading to
CC activation of the protein.
CC -!- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common
CC malignancy in males representing 95% of all testicular neoplasms.
CC TGCTs have various pathologic subtypes including: unclassified
CC intratubular germ cell neoplasia, seminoma (including cases with
CC syncytiotrophoblastic cells), spermatocytic seminoma, embryonal
CC carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. Note=The
CC disease may be caused by mutations affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Inhibition by erlotinib, an orally administered
CC EGFR tyrosine kinase inhibitor used for treatment, enhances STK10-
CC dependent lymphocytic responses, possibly leading to the
CC aggravation of skin inflammation observed upon treatment by
CC erlotinib (PubMed:21606217).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG51143.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AB015718; BAA35073.1; -; mRNA.
DR EMBL; AK022960; BAG51143.1; ALT_INIT; mRNA.
DR EMBL; AK313350; BAG36152.1; -; mRNA.
DR EMBL; AC024561; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW61439.1; -; Genomic_DNA.
DR EMBL; BC070077; AAH70077.1; -; mRNA.
DR EMBL; AL133081; CAB61400.1; -; mRNA.
DR PIR; T42687; T42687.
DR RefSeq; NP_005981.3; NM_005990.3.
DR UniGene; Hs.744005; -.
DR PDB; 2J7T; X-ray; 2.00 A; A=18-317.
DR PDB; 4AOT; X-ray; 2.33 A; A/B=18-317.
DR PDB; 4BC6; X-ray; 2.20 A; A=24-316.
DR PDB; 4EQU; X-ray; 2.00 A; A/B=18-317.
DR PDBsum; 2J7T; -.
DR PDBsum; 4AOT; -.
DR PDBsum; 4BC6; -.
DR PDBsum; 4EQU; -.
DR ProteinModelPortal; O94804; -.
DR SMR; O94804; 24-316.
DR BindingDB; O94804; -.
DR ChEMBL; CHEMBL3981; -.
DR GuidetoPHARMACOLOGY; 2211; -.
DR PhosphoSite; O94804; -.
DR PaxDb; O94804; -.
DR PRIDE; O94804; -.
DR DNASU; 6793; -.
DR Ensembl; ENST00000176763; ENSP00000176763; ENSG00000072786.
DR GeneID; 6793; -.
DR KEGG; hsa:6793; -.
DR UCSC; uc003mbo.1; human.
DR CTD; 6793; -.
DR GeneCards; GC05M171403; -.
DR HGNC; HGNC:11388; STK10.
DR HPA; CAB020840; -.
DR HPA; HPA015083; -.
DR MIM; 273300; phenotype.
DR MIM; 603919; gene.
DR neXtProt; NX_O94804; -.
DR PharmGKB; PA36197; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000236268; -.
DR HOVERGEN; HBG052712; -.
DR InParanoid; O94804; -.
DR KO; K08837; -.
DR OMA; ESMDYGT; -.
DR OrthoDB; EOG7CNZF6; -.
DR SignaLink; O94804; -.
DR ChiTaRS; STK10; human.
DR EvolutionaryTrace; O94804; -.
DR GeneWiki; STK10; -.
DR GenomeRNAi; 6793; -.
DR NextBio; 26535; -.
DR PRO; PR:O94804; -.
DR Bgee; O94804; -.
DR CleanEx; HS_STK10; -.
DR Genevestigator; O94804; -.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042801; F:polo kinase kinase activity; TAS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0071593; P:lymphocyte aggregation; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:2000401; P:regulation of lymphocyte migration; IMP:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR022165; PKK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF12474; PKK; 2.
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 3D-structure; ATP-binding; Cell cycle; Cell membrane; Coiled coil;
KW Complete proteome; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 968 Serine/threonine-protein kinase 10.
FT /FTId=PRO_0000086697.
FT DOMAIN 36 294 Protein kinase.
FT NP_BIND 42 50 ATP (By similarity).
FT REGION 175 224 Activation segment.
FT COILED 573 947 Potential.
FT COMPBIAS 750 884 Gln-rich.
FT ACT_SITE 157 157 Proton acceptor (By similarity).
FT BINDING 65 65 ATP (Probable).
FT BINDING 111 111 Inhibitor.
FT BINDING 113 113 Inhibitor.
FT BINDING 117 117 Inhibitor; via amide nitrogen.
FT BINDING 175 175 Inhibitor.
FT MOD_RES 13 13 Phosphoserine.
FT MOD_RES 185 185 Phosphothreonine.
FT MOD_RES 191 191 Phosphoserine.
FT MOD_RES 438 438 Phosphoserine.
FT MOD_RES 444 444 Phosphoserine.
FT MOD_RES 454 454 Phosphoserine.
FT MOD_RES 549 549 Phosphoserine.
FT MOD_RES 952 952 Phosphothreonine.
FT VARIANT 268 268 R -> C (in dbSNP:rs35826078).
FT /FTId=VAR_041131.
FT VARIANT 277 277 K -> E (in TGCT; somatic mutation).
FT /FTId=VAR_023827.
FT VARIANT 322 322 R -> W (in dbSNP:rs56214442).
FT /FTId=VAR_041132.
FT VARIANT 336 336 T -> I (in dbSNP:rs55972616).
FT /FTId=VAR_041133.
FT VARIANT 467 467 N -> S (in dbSNP:rs56063773).
FT /FTId=VAR_041134.
FT VARIANT 480 480 P -> L (in dbSNP:rs34505340).
FT /FTId=VAR_051671.
FT VARIANT 520 520 P -> L (in dbSNP:rs17074311).
FT /FTId=VAR_051672.
FT VARIANT 710 710 M -> T (in dbSNP:rs34936670).
FT /FTId=VAR_041135.
FT VARIANT 853 853 S -> L (in dbSNP:rs56066852).
FT /FTId=VAR_041136.
FT VARIANT 905 905 S -> T (in dbSNP:rs55791916).
FT /FTId=VAR_041137.
FT VARIANT 942 942 S -> N (in dbSNP:rs1128204).
FT /FTId=VAR_051673.
FT VARIANT 947 947 C -> Y (in dbSNP:rs56355550).
FT /FTId=VAR_041138.
FT MUTAGEN 65 65 K->I: Loss of kinase activity.
FT CONFLICT 62 62 A -> V (in Ref. 5; AAH70077).
FT CONFLICT 136 136 V -> E (in Ref. 5; AAH70077).
FT CONFLICT 317 317 E -> G (in Ref. 5; AAH70077).
FT STRAND 27 30
FT HELIX 32 34
FT STRAND 36 43
FT STRAND 50 55
FT TURN 56 58
FT STRAND 61 67
FT HELIX 75 87
FT STRAND 96 101
FT STRAND 106 111
FT HELIX 118 125
FT HELIX 131 150
FT HELIX 160 162
FT STRAND 163 165
FT STRAND 171 173
FT HELIX 177 187
FT HELIX 196 198
FT HELIX 201 208
FT TURN 212 216
FT HELIX 217 232
FT TURN 236 239
FT HELIX 242 251
FT HELIX 260 262
FT HELIX 265 274
FT TURN 279 281
FT HELIX 285 288
FT TURN 292 296
FT HELIX 301 314
SQ SEQUENCE 968 AA; 112135 MW; 15E245193ECC553D CRC64;
MAFANFRRIL RLSTFEKRKS REYEHVRRDL DPNEVWEIVG ELGDGAFGKV YKAKNKETGA
LAAAKVIETK SEEELEDYIV EIEILATCDH PYIVKLLGAY YHDGKLWIMI EFCPGGAVDA
IMLELDRGLT EPQIQVVCRQ MLEALNFLHS KRIIHRDLKA GNVLMTLEGD IRLADFGVSA
KNLKTLQKRD SFIGTPYWMA PEVVMCETMK DTPYDYKADI WSLGITLIEM AQIEPPHHEL
NPMRVLLKIA KSDPPTLLTP SKWSVEFRDF LKIALDKNPE TRPSAAQLLE HPFVSSITSN
KALRELVAEA KAEVMEEIED GRDEGEEEDA VDAASTLENH TQNSSEVSPP SLNADKPLEE
SPSTPLAPSQ SQDSVNEPCS QPSGDRSLQT TSPPVVAPGN ENGLAVPVPL RKSRPVSMDA
RIQVAQEKQV AEQGGDLSPA ANRSQKASQS RPNSSALETL GGEKLANGSL EPPAQAAPGP
SKRDSDCSSL CTSESMDYGT NLSTDLSLNK EMGSLSIKDP KLYKKTLKRT RKFVVDGVEV
SITTSKIISE DEKKDEEMRF LRRQELRELR LLQKEEHRNQ TQLSNKHELQ LEQMHKRFEQ
EINAKKKFFD TELENLERQQ KQQVEKMEQD HAVRRREEAR RIRLEQDRDY TRFQEQLKLM
KKEVKNEVEK LPRQQRKESM KQKMEEHTQK KQLLDRDFVA KQKEDLELAM KRLTTDNRRE
ICDKERECLM KKQELLRDRE AALWEMEEHQ LQERHQLVKQ QLKDQYFLQR HELLRKHEKE
REQMQRYNQR MIEQLKVRQQ QEKARLPKIQ RSEGKTRMAM YKKSLHINGG GSAAEQREKI
KQFSQQEEKR QKSERLQQQQ KHENQMRDML AQCESNMSEL QQLQNEKCHL LVEHETQKLK
ALDESHNQNL KEWRDKLRPR KKALEEDLNQ KKREQEMFFK LSEEAECPNP STPSKAAKFF
PYSSADAS
//

MIM 273300
*RECORD*
*FIELD* NO
273300
*FIELD* TI
#273300 TESTICULAR GERM CELL TUMOR; TGCT
;;MALE GERM CELL TUMOR; MGCT
SEMINOMA, INCLUDED;;
read moreNONSEMINOMATOUS GERM CELL TUMORS, INCLUDED;;
TERATOMA, TESTICULAR, INCLUDED;;
EMBRYONAL CELL CARCINOMA, INCLUDED;;
ENDODERMAL SINUS TUMOR, INCLUDED;;
SPERMATOCYTIC SEMINOMA, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because testicular germ cell
tumors have been associated with somatic mutation in several genes; see
MOLECULAR GENETICS.

DESCRIPTION

Testicular germ cell tumors (TGCTs) affect 1 in 500 men and are the most
common cancer in males aged 15 to 40 in western European populations.
The incidence of TGCT rose dramatically during the 20th century. Known
risk factors for TGCT include a history of undescended testis (UDT),
testicular dysgenesis, infertility, previously diagnosed TGCT, and a
family history of the disease. Brothers of men with TGCT have an 8- to
10-fold risk of developing TGCT, whereas the relative risk to fathers
and sons is 4-fold. This familial relative risk is much higher than that
for most other types of cancer (summary by Rapley et al., 2000).

- Genetic Heterogeneity of Testicular Germ Cell Tumors

A locus for testicular germ cell tumors (TGCT1; 300228) has been
identified on chromosome Xq27.

CLINICAL FEATURES

Hutter et al. (1967) reviewed the reports of testicular tumors in
brothers and in twins and reported affected brothers.

Gustavson et al. (1975) reported bilateral testicular teratoma in 2
infant brothers with XXY Klinefelter syndrome. One of them also had
hydrocephalus due to stenosis of the aqueduct of Sylvius. Familial
occurrence of the Klinefelter syndrome is rare. The association of the
Klinefelter syndrome and testicular teratoma may be more than
coincidental because they have been observed together in other cases and
many testicular teratoma are both X-chromatin and Y-chromatin positive
suggesting that they are XXY.

Raghavan et al. (1980) reported a father who had sequential bilateral
seminomas and a son who had embryonal cell carcinoma and seminoma. The
authors reviewed 5 other reports of testicular tumors in father and son,
as well as 7 reports of concordant monozygotic twin pairs and 11 reports
of nontwin brothers. The report of Raghavan et al. (1980) illustrates
the dominant inheritance of hereditary tumors and their bilaterality
(e.g., acoustic neuroma, retinoblastoma, pheochromocytoma, etc.). The
sons (and other first-degree relatives) of men with bilateral tumors may
be at particular risk.

Shinohara et al. (1980) reported mature testicular teratoma in 2 first
cousins. Furthermore, the common grandparents were consanguineous, being
related as first cousins. The parent (i.e., the parent involved in the
consanguinity) of the teratoma-carrying boys was the mother in one case
and the father in the other. In a 10-member sibship in a
Spanish-American family, DiBella (1983) described testicular neoplasm in
3 brothers, benign ovarian neoplasms in 2 sisters, suspected benign
tumors of the uterus in 2 additional sisters, and a suspected testicular
mass in a fourth brother. Lynch et al. (1985) described the infantile
form of embryonal carcinoma of the testis in a 5-year-old boy and in a
23-year-old man who was the maternal half brother of his mother.
Copeland et al. (1986) reported testicular embryonal carcinoma in 2
brothers and a first cousin.

Von der Maase et al. (1986) found carcinoma in situ in the contralateral
testis in 27 of 500 patients (5.4%) with unilateral testicular germ cell
cancer. The estimated risk of developing invasive growth from the
contralateral testicular cancer was 40% within 3 years and 50% within 5
years. None of the 473 patients without carcinoma in situ detected by
screening biopsy developed contralateral testicular cancer after an
observation time ranging from 12 to 96 months. These observations
suggested to the authors that there is a subset of this type of
testicular cancer that is genetic and has a bilateral predisposition.
The authors suggested that all such carcinomas begin as carcinoma in
situ. Von der Maase et al. (1986) recommended that all patients with
unilateral testicular germ cell cancer should be offered biopsy of the
contralateral testis. Of the 27 patients, 16 had a cancer that was
labeled seminoma and 11 had a cancer that was considered to be
nonseminoma. It would be of great interest to know the median age of the
patients with contralateral carcinoma in situ as contrasted with the
others. If these represent a subset who had inherited 1 of the 2
mutations according to the Knudson theory, then the patients with
contralateral carcinoma in situ should have an earlier average age of
development of carcinoma.

Patel et al. (1990) reported 6 cases of familial testicular cancer: 4
father-son pairs, a pair of brothers, and a 23-year-old man who had a
maternal uncle with testicular cancer. In the U.K., according to Forman
et al. (1992), 42 families with 2 or more cases of testicular cancer
were reported to the familial testicular cancer registry. These families
included 2 pairs of identical twins, 27 sets of other brothers (25
pairs, 2 triples), 9 father-son pairs, 2 pairs of first cousins, and 2
uncle-nephew pairs. In all, 91 testicular tumors were described in 86
persons. Pure seminoma was present in 46% and other germ cell tumors in
54%. The median age at diagnosis was significantly younger than in a
comparable series of nonfamilial patients. The cumulative risk of
developing testicular cancer by the age of 50 years for a brother of a
patient was estimated to be 2.2%, which results in a relative risk of
9.8 in comparison with the general population. No significant
peculiarity of class I HLA type was found in a study of 21 affected sib
pairs.

Huddart et al.(1996) studied 3 families suggesting that there is a
familial predisposition to both male and female germ cell tumors. In 1,
the proband presented with a seminoma at the age of 51, his brother had
had a testicular teratoma at the age of 28, and their cousin had an
endodermal sinus tumor of the ovary diagnosed at 32 years. In the second
family, the index case presented with an undifferentiated malignant
teratoma at 28 years of age and his sister was diagnosed with bilateral
mature teratomatous cysts at the age of 39. In the third family, the
index case presented with a retroperitoneal teratoma at 26 years and his
sister was diagnosed with an ovarian dysgerminoma at 45 years. Huddart
et al. (1996) noted that none of these families had any features
indicative of the Li-Fraumeni syndrome (151623) or any other cancer
family syndrome. Trentini and Palmieri (1974) and Yule et al. (1994)
reported single families with ovarian and testicular germ cell tumors
and Jackson (1967) presented a family with multiple cases of
dysgerminoma.

Greene et al. (2010) noted that in familial cases the most common number
of affected family members was 2, that age at diagnosis was 2 to 3 years
younger for familial versus sporadic cases, and that familial TGCT were
more likely to be bilateral than sporadic TGCT.

- Association with Testicular Microlithiasis

Coffey et al. (2007) analyzed the frequency of testicular microlithiasis
(TM; 610441) in 169 patients with testicular germ cell tumor (TGCT), 58
relatives, and 101 controls and found that TM was more frequent in
unaffected male relatives of TGCT cases than controls and that patients
with a history of TGCT had a higher frequency of TM in their
contralateral remaining testis than controls. Coffey et al. (2007) also
demonstrated significant concordance of TM between relatives, raising
the hypothesis that TGCT and TM have a joint etiology.

Korde et al. (2008) performed testicular ultrasound in 48 men with
familial testicular cancer from 31 families with at least 2 cases of
TGCT, and in 33 of their unaffected male relatives. Testicular
microlithiasis (TM) was more frequent in the contralateral testicles of
men with a history of TGCT than in unaffected men (48% vs 24%; p =
0.04). The association appeared stronger for men with 5 or more
microliths than for those with less than 5 microliths. Testicular
microlithiases were bilateral in 6 (75%) of the 8 unaffected men in whom
they were detected. Among affected men, TM was not associated with
histology, age at diagnosis, or cancer treatment. Korde et al. (2008)
noted that TM was more prevalent among unaffected family members in this
study (24%) than previously described in the general population (0.6 to
9%), and that it appeared to cluster in certain families. The findings
suggested both a familial predisposition to TM and an association
between TM and TGCT.

POPULATION GENETICS

Forman et al. (1992) reported an epidemiologic study that showed an 8-
to 10-fold increase in relative risk of testicular cancer to brothers of
patients and a 4-fold increase in risk to fathers and sons. Families
with multiple cases of testicular cancer are rare and almost all those
reported have only 2 affected members.

Heimdal et al. (1996) found that 51 of 922 (5.5%) Norwegian patients
with testicular cancer and 5 of 237 (2.1%) Swedish patients had a
relative with confirmed testicular cancer. It was a first-degree
relative who was affected in the case of 32 of the probands.
Standardized incidence ratios (SIRs) were 10.2 for brothers, 4.3 for
fathers, and 5.7 for sons. The estimate for the risk to brothers in the
Norwegian part of the sample for development of testicular cancer by the
age of 60 was 4.1%. Patients with familial testicular cancer had
bilateral tumors more often than sporadic cases (9.8% bilaterality in
familial vs 2.8% in sporadic cases; P = 0.02). For patients with
seminoma, age of onset was lower in familial than in sporadic cases
(32.9 vs 37.6 years; P = 0.06). Heimdal et al. (1996) stated that the
prevalence of undescended testis did not seem to be higher in familial
than in sporadic testicular cancer.

Einhorn (2002) stated that the highest worldwide incidence of germ cell
tumors is in Scandinavian countries; by contrast, testicular cancer is
rare in African Americans. The primary age group is 15 to 35 years for
nonseminomatous tumors and a decade older for seminomas. Although cases
are few, germ cell tumors are important because they represent the most
common carcinoma in men aged 15 to 35 years and thus have the potential
to greatly shorten productive years of life. Available serum markers
such as alphafetoprotein (104150) and human chorionic gonadotropin have
allowed clinicians to make important and accurate treatment-related
decisions. Testicular cancer is a model for multidisciplinary care, as
surgical resection of postchemotherapy radiographically persistent
disease can improve the cure rate. Germ cell tumors have become an
excellent testing ground for experimental drugs, a number of which were
first approved by the Food and Drug Administration primarily on the
basis of data in testicular cancer.

INHERITANCE

Greene et al. (2010) reviewed the genetic risk factors and clinical
phenotype of familial testicular germ cell tumors in adults, noting that
although linkage analyses had identified several genomic regions of
modest interest, no high-penetrance cancer susceptibility gene had been
mapped to date, suggesting that the combined effects of multiple common
alleles, each conferring modest risk, might underlie familial testicular
cancer.

- L1 Methylation Status

Mirabello et al. (2010) studied global methylation at long interspersed
nuclear elements-1 (L1; 151626) in DNA from 152 patients with TGCT and
314 unaffected family members from 101 multiple-case testicular cancer
families. Analysis of the correlation of L1 methylation levels among
parent-child pairs independent of affection status revealed a strong
positive association only between mother-daughter (r = 0.48; p = 0.0002)
and father-daughter (r = 0.31; p = 0.021) pairs, suggesting
gender-specific inheritance of methylation. Incorporating cancer status
into the analysis revealed a strong correlation in L1 methylation levels
only among affected father-son pairs (r = 0.49; p = 0.03). There was a
marginally significant inverse association between lower L1 methylation
levels and increased risk of TGCT, compared to healthy male relatives (p
= 0.049). Mirabello et al. (2010) stated that their findings suggested
that heritability of L1 methylation might be gender-specific, and that
transgenerational inheritance of L1 methylation levels might be
associated with testicular cancer risk.

CYTOGENETICS

Studying direct preparations and 24-hr cultures, Atkin and Baker (1982)
found an isochromosome for the short arm of chromosome 12 in all of 10
seminomas, 1 malignant teratoma, and 1 combined seminoma and teratoma of
the testis. (The same workers found a possible isochromosome for 5p in
12 of 18 carcinomas of the cervix.) They also noted a relative excess of
normal chromosomes 12 in 4 of 5 of the seminomas analyzed in detail.
Castedo et al. (1989) found at least 1 copy of a 12p isochromosome in 8
of 10 seminomas. Thus, the authors concluded that amplification of 1 or
more genes on the short arm of chromosome 12 may be important in the
development of malignant testicular tumors. Chromosomal changes
presumably lead to the malignant phenotype by gene loss, gene
modification or gene amplification.

Samaniego et al. (1990) analyzed the karyotype of 24 male germ cell
tumors from both testicular and extragonadal sites and belonging to the
histologic categories seminoma, teratoma, embryonal carcinoma,
choriocarcinoma, and endodermal sinus tumor. In 90% of tumors, including
all histologic subtypes and both gonadal and extragonadal presentation,
they found isochromosome 12p. In contrast, they found del(12)(q13-q22)
exclusively in nonseminomatous GCTs, and mixed GCTs occurring in 44% of
such lesions. They developed a method based on DNA analysis for
detecting i(12p) as increased copy number of 12p. Furthermore, they
detected cytologic evidence of gene amplification in 12p in the form of
homogeneously staining regions (HSRs) and double minute chromosomes in
both treated and untreated primary extragonadal and metastatic GCTs.

Suijkerbuijk et al. (1991, 1992) applied competitive in situ
hybridization (CISH) techniques (Kievits et al., 1990) to show that the
aberrant chromosome in testicular germ cell tumors is indeed an
isochromosome 12p. Other marker chromosomes representing translocation
products that involve chromosome 12 were also identified. In the
studies, DNAs from 2 rodent-human somatic cell hybrids, containing
either a normal chromosome 12 or the p arm of chromosome 12 as their
unique human material, were used as probes. (Competitive in situ
hybridization, also referred to as chromosome painting, employs large
pools of cloned genomic sequences originating from a single human
chromosome as probe and involves a preannealing step in the presence of
an excess of sonicated total human DNA. It results in complete staining
of the particular chromosome in metaphase spreads and in interphase
nuclei. Kievits et al., 1990 stated that the approach permits detection
of hitherto undetectable chromosomal aberrations.)

In a cytogenetic analysis of 65 consecutively ascertained GCTs with
chromosomal abnormalities, Rodriguez et al. (1992) found that an
isochromosome for the short arm of chromosome 12 (i(12p)), monosomy 12,
and deletions in 12q occurred with frequencies of 86%, 11%, and 20%
respectively.

Because a marker chromosome interpreted as isochromosome 12p is present
in most testicular tumors of germ cell origin, Peltomaki et al. (1992)
investigated 22 patients with testicular germ cell tumors by Southern
blot hybridization to characterize changes in chromosome 12. In
comparison with normal DNA, tumor DNA of 18 patients showed increased
dosages of 12p accompanied by a comparable or smaller increase or no
change in the dosage of centromeric sequences of chromosome 12. The
interpretation offered by the authors was that most testicular tumors
had one or several isochromosomes for 12p that were formed by somatic
division of the centromere and that the points of breakage and reunion
in the centromeric region were different in different tumors.
Sex-limited parental imprinting was excluded by the fact that allelic
12p fragments showing increased intensity were paternal in 4 and
maternal in 3 of 7 informative cases. Furthermore, the observed patterns
of allelic fragments suggested that the marker isochromosome was formed
by sister chromatids of 1 homolog number 12 rather than the result of
interchange of genetic material between different homologs.

Ottesen et al. (2004) studied 3 brothers with germ cell tumors. One had
an intracranial tumor in the pineal region and the other 2 had
testicular tumors. No abnormalities were detected in peripheral blood
with karyotyping and molecular marker analysis of selected loci.
High-resolution comparative genomic hybridization (CGH) analysis of
microdissected histologic components of the overt tumors and the
adjacent carcinoma in situ demonstrated a pattern of genomic imbalances
characteristic for sporadic GCTs, including gain of 12p.

Stadler et al. (2012) investigated germline de novo copy number
variations (CNVs) in 382 genomes of 116 early-onset cancer case parent
trios and unaffected sibs. Unique de novo germline CNVs were not
observed in 107 breast or colon cancer trios or controls but were found
in 7% of 43 testicular germ cell tumor trios; this percentage exceeded
background CNV rates and suggested a rare de novo genetic paradigm for
susceptibility to some human malignancies.

MAPPING

- Genomewide Association Studies

Leahy et al. (1995) performed a sib-pair analysis on 35 families in
which there were either 2 or 3 affected brothers. These families were
typed for 220 autosomal microsatellite markers spaced 10-20 cM
throughout the genome. Six regions that gave a lod score of more than
1.0 on formal linkage analysis or a p value of 0.05 or less using a
nonparametric approach were considered as candidate regions for a
susceptibility gene. Of particular interest was one region on chromosome
4. A positive lod score of 2.6 on multipoint analysis was obtained with
2 neighboring probes in the region of 4cen-q13.

Rapley et al. (2009) performed a genomewide association study involving
730 TGCT cases and 1,435 controls, with replication in 571 cases and
1,806 controls, and found the strongest evidence for association with
dbSNP rs995030 (OR, 2.55; p = 1.0 x 10(-31)) and dbSNP rs1508595 (OR,
2.69; p = 2.6 x 10(-30)) that are both located within the same linkage
disequilibrium block on chromosome 12q22. Rapley et al. (2009) noted
that this region contains only 1 annotated protein-coding gene, KITLG
(184745), encoding the ligand for KIT, which has previously been
implicated in the pathogenesis of TGCT. There was also evidence for
susceptibility loci at dbSNP rs4624820 located 10-kb 3-prime of the
SPRY4 gene (607984) on chromosome 5q31.3 (per-allele odds ratio, 1.37; p
= 3.3 x 10(-13)) and at dbSNP rs210138 located in an intron of the BAK1
gene (600516) on chromosome 6p21.3-p21.2 (OR, 1.50; p = 1.1 x 10(-13)).

In a genomewide scan involving 277 TGCT cases and 919 controls, Kanetsky
et al. (2009) found 7 markers at chromosome 12q22 within the KITLG gene
that reached genomewide significance (p less than 5.0 x 10(-8)); in
independent replication using 371 TGCT cases and 860 controls, TGCT risk
increased 3-fold per copy of the major allele at dbSNP rs3782179 and
dbSNP rs4474514. The markers were associated with both seminoma and
nonseminoma TGCT subtypes.

Turnbull et al. (2010) conducted a genomewide association study for
testicular germ cell tumor, genotyping 298,782 SNPs in 979 affected
individuals and 4,947 controls from the U.K. and replicating
associations in a further 664 cases and 3,456 controls. Turnbull et al.
(2010) identified 3 novel susceptibility loci, 2 of which include genes
that are involved in telomere regulation. They identified 2 independent
signals within the TERT (187270)-CLPTM1L (612585) locus on chromosome
5p15.33, which had been associated with multiple other cancers (dbSNP
rs4635969, OR = 1.54, P = 1.14 x 10(-23); dbSNP rs2736100, OR = 1.33, P
= 7.55 x 10(-15)). Turnbull et al. (2010) also identified a locus on
chromosome 12 (dbSNP rs2900333, OR = 1.27, P = 6.16 x 10(-10)) that
contains ATF7IP, a regulator of TERT expression. Finally, Turnbull et
al. (2010) identified a locus on chromosome 9p24.3 (dbSNP rs755383, OR =
1.37, P = 1.12 x 10(-23)), containing the sex determination gene DMRT1
(602424), which has been linked to teratoma susceptibility in mice.

- Other Mapping Studies

Lothe et al. (1989) found loss of heterozygosity (LOH) for 3p or 11p
sequences in 40% of testicular cancers.

Mathew et al. (1994) analyzed chromosome 1 loss of heterozygosity in a
panel of 48 GCTs and observed allelic losses in 46% of cases on 1p and
in 23% of cases on 1q. There were 4 sites of frequent deletions, 3 in
the short arm (1p13, 1p22, and 1p32.2-p31.3) and 1 in the long arm
(1q32). Of the 11 probes on 1p that showed allelic losses, the highest
frequency of LOH was observed for D1S16 at 1p22 (38.5%). Teratomas
showed higher frequency of allelic losses (24.4%) compared to embryonal
carcinomas (9.5%), yolk sac tumors (12.1%), or seminomas (7.6%).

Rodriguez et al. (1992) presented data strongly suggested that loss of
genetic material on 12q characterizes the development of TGCTs. To
define the region of common deletion in GCTs at the molecular level,
Murty et al. (1992) compared germline and tumor genotypes for 8
polymorphic loci in paired normal/tumor DNA samples from 45 GCT
patients. Analysis demonstrated 2 regions of loss of constitutional
heterozygosity, one at 12q13 and the other at 12q22. One tumor exhibited
homozygous deletion of a region of 12q22 which includes the MGF gene
(184745). The MGF and KIT (164920) genes have been shown to play key
roles in embryonal and postnatal development of germ cells. The MGF gene
product constitutes the ligand for the receptor encoded by the KIT
protooncogene. They evaluated the expression of these 2 genes by
Northern blot analysis in a panel of 3 GCT cell lines and 24 fresh GCT
biopsies. Deregulated expression of MGF and KIT, which was discordant
between seminomatous and nonseminomatous lesions, was observed. Murty et
al. (1994) refined their data on the mapping of male germ cell tumors
(MGCTs). Using 5 dinucleotide repeats mapping to 12q22, they found LOH
in approximately 41% of tumors; one of the loci, D12S218, showed LOH in
37% of tumors, suggesting the presence of a tumor suppressor gene in its
vicinity. In this study, a panel of 66 tumor DNA samples and their
corresponding normal cells were investigated.

In a detailed deletion mapping analysis of 67 normal-tumor DNA
comparisons using 20 polymorphic markers mapped to 12q22-q24, Murty et
al. (1996) identified the limit of the minimal region of deletion at
12q22 between D12S377 (proximal) and D12S296 (distal). They constructed
a YAC contig map of a 3-cM region of this band and developed a radiation
hybrid (RH) map of the region. The consensus order developed by RH
mapping was in good agreement with the YAC STS-content map order. The RH
map estimated the distance between the D12S101 and D12S346 to be 246
cR(8000) and the minimal region of deletion to be 141 cR(8000).

Murty and Chaganti (1998) reviewed the genetics of male germ cell
tumors. A characteristic of GCTs is high sensitivity to cisplatin-based
chemotherapy. Chromosomal and molecular cytogenetic studies identified
multiplication of 12p, manifested in i(12p) or tandem duplication of
12p, as a unique change in GCTs which serves as a diagnostic marker.
Ectopic overexpression of cyclin D2 (CCND2; 123833), which maps to 12p,
as early as in carcinoma in situ, identified CCND2 as a candidate gene
in germ cell transformation. Genetic alterations identified in the tumor
suppressor genes DCC (120470), RB1 (614041), and nonmetastatic
protein-23 (NME1; 156490) in GCTs suggested that their inactivation
plays a key role in transformation or differentiation. The exquisite
sensitivity of these tumors to chemotherapy is reflected in their
overexpression of wildtype p53 protein and lack of TP53 mutations.

Zafarana et al. (2002) identified the DADR (609860), SOX5 (604975), and
ETNK1 (609858) genes within a region of chromosome 12p amplified in
testicular seminomas. Although all 3 genes were amplified to the same
level in seminomas with the amplification, only DADR expression was
significantly upregulated. DADR was also highly expressed in
nonseminomas of various histologies and derived cell lines lacking the
12p amplification. Low DADR expression was observed in normal testicular
parenchyma and in parenchyma containing carcinoma in situ. DADR
overexpression in seminomas and nonseminomas correlated with invasive
growth, reduced apoptosis, and earlier clinical manifestation.

In 97 patients with familial TGCT, 22 patients with sporadic bilateral
TGCT, and 871 controls, Kratz et al. (2011) genotyped 106 SNPs in 4
regions, in or near BAK1 on 6p21, DMRT1 on 9p24, KITLG on 12q, and
TERT-CLPTM1L on 5p15, all of which had previously been identified in
genomewide association studies of TGCT. Three previously identified risk
SNPs were replicated in the familial and sporadic bilateral TGCT
patients: dbSNP rs210138 within an intron of BAK1 (OR, 1.80; p = 7.03 x
10(-5)), dbSNP rs755383 near DMRT1 (OR, 1.67; p = 6.70 x 10 (-4)), and
dbSNP rs4635969 near TERT-CLPTM1L (OR, 1.59; p = 4.07 x 10(-3)).
Evidence for a second independent association was found for a SNP within
an intron of TERT, dbSNP rs4975605 (OR, 1.68; p = 1.24 x 10(-3)). In
addition, an association with another SNP in KITLG, dbSNP rs2046971, was
identified (OR 2.33; p = 1.28 x 10(-3)); this SNP is in high linkage
disequilibrium with the previously reported risk variant dbSNP rs995030.
Kratz et al. (2011) suggested that familial TGCT and sporadic bilateral
TGCT are polygenetic diseases caused by the same spectrum of genetic
risk factors.

- Y-Chromosome Microdeletion

A 1.6-Mb deletion of the Y chromosome that removes part of the AZFc
region--known as the gr/gr deletion (see 415000)--has been associated
with infertility. In epidemiologic studies, male infertility has shown
an association with testicular germ cell tumor (TGCT) that is out of
proportion with what can be explained by tumor effects. Thus, Nathanson
et al. (2005) hypothesized that the gr/gr deletion may be associated
with TGCT. They analyzed this deletion in a large series of TGCT cases
with or without a family history of TGCT. The gr/gr deletion was present
in 3% of TGCT cases with a family history. 2% of TGCT cases without a
family history, and 1.3% of unaffected males. The presence of the gr/gr
deletion was associated with a 2-fold increased risk of TGCT and a
3-fold increased risk of TGCT among patients with a positive family
history. The gr/gr deletion was more strongly associated with seminoma
TGCT than with nonseminoma TGCT. Thus, the Y microdeletion gr/gr appears
to be a rare, low penetrance allele that confers susceptibility to TGCT.

MOLECULAR GENETICS

- Variation in the BCL10 Gene and Progression to Advanced
Stage TGCT

Inoue et al. (2006) analyzed 4 SNPs in the BCL10 gene on chromosome
1p22, which had previously been identified in Japanese TGCTs by Kakinuma
et al. (2001), in 73 TGCT patients and 72 controls. No significant
difference in any of the 4 SNPs was observed between patients and
controls. However, GCT patients with metastatic disease were more likely
than patients with only local disease to carry a minor allele of either
of 2 SNPs in exon 1: 13G-T (A5S; adjusted odds ratio, 6.25, and p =
0.040) or 24C-G (L8L; adjusted odds ratio, 4.63 and p = 0.015). Inoue et
al. (2006) concluded that these BCL10 polymorphisms in exon 1 might play
a role in progression to advanced stage TGCTs.

- Somatic Mutation in the BLC10 Gene on Chromosome 1p22

Willis et al. (1999) analyzed 3 male germ cell tumor lines (Tera1,
Tera2, and GCT44) and identified 2, 3, and 1 mutations in the BCL10 gene
(603517), respectively (see, e.g., 603517.0001, 603517.0016, and
603517.0017).

Fakruddin et al. (1999) sequenced BCL10 in the 3 GCT cell lines
previously studied by Willis et al., 1999 but found no mutations.
Fakruddin et al. (1999) noted that their data were at variance with the
results reported by Willis et al. (1999), and concluded that BCL10 is
not a target tumor suppressor gene at 1p22 in GCTs.

Van Schothorst et al. (1999) screened exons 2 and 3 of the BCL10 gene in
a series of TGCT-derived and related cell lines, including the 3 GCT
cell lines previously studied by Willis et al., 1999, as well as primary
tumors. No aberrations were detected by SSCP on genomic DNA or
restriction endonuclease digestion analysis of PCR-amplified fragments,
and van Schothorst et al. (1999) concluded that inactivation of BCL10 by
genomic events in TGCTs is not involved in the majority of cases, if at
all.

Lee et al. (1999) analyzed the BCL10 gene by PCR-SSCP using DNA
extracted from malignant and normal cells of 439 paraffin-embedded tumor
tissue samples, including 78 GCTs. Enrichment and direct sequencing of
aberrantly migrating bands led to the identification of somatic
mutations in 2 (2.6%) of the 78 TGCTs (both were mature teratomas; see,
e.g., 603517.0018). Lee et al. (1999) concluded that BCL10 may
occasionally be involved in the pathogenesis of TGCTs, but that the
absence or low frequency of mutation suggested that either BCL10 is
inactivated by other mechanisms or that it is not the only target of
chromosome 1p22 deletion in human tumors.

Kakinuma et al. (2001) found loss of heterozygosity at chromosome 1p in
21 (42%) of 49 Japanese TGCTs, including 12 (43%) of 28 seminomas and 8
(38%) of 21 nonseminomatous GCTs. No somatic mutations were identified
by SSCP and direct sequencing in any of the tumors, although 4 SNPs were
detected.

- Somatic Mutation in the FGFR3 Gene on Chromosome 4p16

Goriely et al. (2009) screened 30 spermatocytic seminomas for oncogenic
mutations in 17 genes and identified a K650E mutation in FGFR3
(134934.0004) in 2 tumors.

- Somatic Mutation in the KIT Gene on Chromosome 4q12

Tian et al. (1999) identified an asp816-to-his mutation in the KIT gene
(164920.0021) in primary tissue samples from patients with germ cell
tumors.

- Somatic Mutation in the BRAF Gene on Chromosome 7q34

Sommerer et al. (2005) analyzed the BRAF gene (164757) in 30 seminomas
and 32 nonseminomatous GCTs with a mixture of embryonal carcinoma, yolk
sac tumor, choriocarcinoma, and mature teratoma. The activating BRAF
missense mutation 1796T-A (164757.0001) was identified in 3 (9%) of 32
nonseminomatous tumors, within the embryonic carcinoma component; no
BRAF mutations were found in the seminomas. There was no correlation
between BRAF mutation status and tumor stage or grade or other
histopathologic factors.

- Somatic Mutation in the HRAS Gene on Chromosome 11p15.5

Goriely et al. (2009) screened 30 spermatocytic seminomas for oncogenic
mutations in 17 candidate genes and identified apparent homozygosity for
5 mutations in the HRAS gene (190020), 3 182A-G transitions and 2 181C-A
transversions, all involving the Q61 codon (see, e.g., 190020.0002).

- Somatic Mutation in the KRAS Gene on Chromosome 12p12

Sommerer et al. (2005) analyzed the KRAS gene (190070) in 30 seminomas
and 32 nonseminomatous GCTs with a mixture of embryonal carcinoma, yolk
sac tumor, choriocarcinoma, and mature teratoma. KRAS mutations, all
involving codon 12, were identified in 2 (7%) of 30 seminomas and 3 (9%)
of 32 nonseminomas. The KRAS mutations in the nonseminomas occurred
within the embryonal carcinoma component in 2 and within the
choriocarcinoma in 1. No correlation between KRAS mutation pattern and
histopathologic variables was observed.

- Somatic Mutation in the STK11 Gene on Chromosome 19p13

Avizienyte et al. (1998) identified a somatic gly163-to-asp mutation in
the STK11 gene (602216.0011) in a case of sporadic testicular carcinoma.

- Exclusion Studies

Murty et al. (1996) excluded 4 genes on chromosome 12q22 as candidates
for familial testicular cancer: mast cell growth factor (184745), B-cell
translocation gene-1 (109580), thymopoietin (188380), and neural
precursor cell expressed, developmentally down-regulated-1 (600372).

ANIMAL MODEL

In laboratory mice, testicular germ cell tumors (TGCTs) arise from
primordial germ cells (PGC) in only the inbred 129 strain, and
susceptibility is under multigenic control (Stevens and Hummel, 1957).
The spontaneously arising mutation Ter (Stevens, 1973) on mouse
chromosome 18 (Asada et al., 1994; Sakurai et al., 1994) increases TGCT
frequency on a 129/Sv background.

Inbred 129 strain mice are predisposed to developing male germ cell
tumors (GCTs) of the testes. GTC incidence is increased in 129 strain
males that lack functional p53 protein (191170). Muller et al. (2000)
used this finding to facilitate the generation of panels of GCT-bearing
intercross and backcross mice for genetic mapping analysis. A 129 strain
locus, designated pgct1, that segregated with the male GCT phenotype was
identified on mouse chromosome 13 near D13Mit188. This region of mouse
chromosome 13 may have conservation of synteny with a portion of human
chromosome 5q that is implicated in male GCT susceptibility in humans.

Youngren et al. (2005) reported the positional cloning of Ter, revealing
a point mutation that introduces a termination codon in the mouse Dnd1
gene (609385). PGC deficiency was corrected both with BACs containing
Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal
gonads during the critical period when TGCTs originate. Dnd1 has an RNA
recognition motif and is most similar to the apobec (see 600130)
complementation factor, a component of the cytidine to uridine RNA
editing complex. These results suggested that Ter may adversely affect
essential aspects of RNA biology during PGC development. Youngren et al.
(2005) stated that Dnd1 was the first protein known to have an RNA
recognition motif directly implicated as a heritable cause of
spontaneous tumorigenesis, and they suggested that TGCT development in
the 129-Ter mouse strain models pediatric TGCTs in humans.

Collin et al. (1996), in a genome scan of tumor-bearing progeny from
backcrosses between the 129/Sv-Ter/+ and MOLF/Ei strains provided modest
evidence that MOLF-derived alleles on mouse chromosome 19 enhance
development of bilateral TGCTs. To obtain independent evidence for
linkage to the MOLF chromosome, Matin et al. (1999) made an autosomal
chromosome substitution strain (a so-called consomic strain, or CSS), in
which chromosome 19 of 129/Sv +/+ was replaced by its MOLF-derived
homolog. The unusually high frequency of TGCTs in this CSS (even in the
absence of the Ter mutation) provided evidence confirming the genome
survey results, identified linkage for a naturally occurring strain
variant allele that confers susceptibility to TGCTs, and illustrated the
power of CSSs in complex trait analysis.

The agouti (ASIP; 600201)-yellow (Ay) deletion is the only genetic
modifier known to suppress testicular germ cell tumor (TGCT)
susceptibility in mice or human. The Ay mutation deletes Raly and Eif2s2
(603908) and induces the ectopic expression of agouti, all of which are
potential TGCT-modifying mutations. Heaney et al. (2009) reported that
the reduced TGCT incidence of heterozygous Ay male mice and the
recessive embryonic lethality of Ay are caused by the deletion of
Eif2s2, the beta subunit of translation initiation factor eIF2. The
incidence of affected males was reduced 2-fold in mice that were
partially deficient for Eif2s2 and that embryonic lethality occurred
near the time of implantation in mice that were fully deficient for
Eif2s2. In contrast, neither reduced expression of Raly in gene-trap
mice nor ectopic expression of agouti in transgenic or viable-yellow
(Avy) mutants affected TGCT incidence or embryonic viability. Partial
deficiency of Eif2s2 attenuated germ cell proliferation and
differentiation, both of which are important to TGCT formation. Heaney
et al. (2009) concluded that germ cell development and TGCT pathogenesis
are sensitive to the availability of the eIF2 translation initiation
complex and to changes in the rate of translation.

*FIELD* SA
Zevallos et al. (1983)
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59. von der Maase, H.; Rorth, M.; Walbom-Jorgensen, S.; Sorensen,
B. L.; Christophersen, I. S.; Hald, T.; Jacobsen, G. K.; Berthelsen,
J. G.; Skakkebaek, N. E.: Carcinoma in situ of contralateral testis
in patients with testicular germ cell cancer: study of 27 cases in
500 patients. Br. Med. J. (Clin. Res. Ed.) 293: 1398-1401, 1986.

60. Willis, T. G.; Jadayel, D. M.; Du, M.-Q.; Peng, H.; Perry, A.
R.; Abdul-Rauf, M.; Price, H.; Karran, L.; Majekodunmi, O.; Wlodarska,
I.; Pan, L.; Crook, T.; Hamoudi, R.; Isaacson, P. G.; Dyer, M. J.
S.: Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma
and mutated in multiple tumor types Cell 96: 35-45, 1999.

61. Youngren, K. K.; Coveney, D.; Peng, X.; Bhattacharya, C.; Schmidt,
L. S.; Nickerson, M. L.; Lamb, B. T.; Deng, J. M.; Behringer, R. R.;
Capel, B.; Rubin, E. M.; Nadeau, J. H.; Matin, A.: The Ter mutation
in the dead end gene causes germ cell loss and testicular germ cell
tumours. Nature 435: 360-364, 2005.

62. Yule, S. M.; Dawes, P. J.; Malcolm, A. J.; Pearson, A. D.: Occurrence
of seminoma and dysgerminoma in father and daughter. Pediat. Hemat.
Oncol. 11: 211-213, 1994.

63. Zafarana, G.; Gillis, A. J. M.; van Gurp, R. J. H. L. M.; Olsson,
P. G.; Elstrodt, F.; Stoop, H.; Millan, J. L.; Oosterhuis, J. W.;
Looijenga, L. H. J.: Coamplification of DAD-R, SOX5, and EKI1 in
human testicular seminomas, with specific overexpression of DAD-R,
correlates with reduced levels of apoptosis and earlier clinical manifestation. Cancer
Res. 62: 1822-1831, 2002.

64. Zevallos, M.; Snyder, R. N.; Sadoff, L.; Cooper, J. F.: Testicular
neoplasm in identical twins: a case report. JAMA 250: 645-646, 1983.

*FIELD* CS
INHERITANCE:
Isolated cases

GENITOURINARY:
[Internal genitalia, male];
Painless testicular mass

NEOPLASIA:
Male germ cell tumors (GCT), 2 subtypes -;
Seminoma;
Nonseminoma (embryonal carcinoma, teratoma, choriocarcinoma, endodermal
sinus tumor)

LABORATORY ABNORMALITIES:
Isochromosome 12p (i(12p));
Elevated hCG (choriocarcinoma);
Elevated AFP (endodermal sinus tumor);
Elevated hCG or AFP or both (embryonal carcinoma);
Azoospermia/oligospermia (present at diagnosis)

MISCELLANEOUS:
Two subtypes - seminoma and nonseminoma;
Occasionally germ cell tumor arise from extra gonadal site (e.g.,
mediastinum, retroperitoneum, pineal gland);
Most common cancer in men aged 15-40 years;
Highest incidence in men of European descent;
Risk factors for development of TGCT - family history, cryptorchidism
(219050), testicular feminization (300068), Klinefelter syndrome,
previous TGCT, gonadal dysgenesis

*FIELD* CN
Kelly A. Przylepa - revised: 5/12/2006

*FIELD* CD
John F. Jackson: 6/15/1995

*FIELD* ED
joanna: 09/10/2012
joanna: 2/1/2007
joanna: 5/12/2006
alopez: 12/19/2005

*FIELD* CN
Ada Hamosh - updated: 10/15/2013
Marla J. F. O'Neill - updated: 11/29/2011
Marla J. F. O'Neill - updated: 11/23/2011
Marla J. F. O'Neill - updated: 8/3/2011
Ada Hamosh - updated: 11/10/2010
George E. Tiller - updated: 11/25/2009
Marla J. F. O'Neill - updated: 9/10/2009
Marla J. F. O'Neill - updated: 8/10/2009
Patricia A. Hartz - updated: 1/30/2006
Victor A. McKusick - updated: 12/12/2005
Ada Hamosh - updated: 6/3/2005
Victor A. McKusick - updated: 2/25/2004
Victor A. McKusick - updated: 10/11/2002
Victor A. McKusick - updated: 9/29/1999
Victor A. McKusick - updated: 8/21/1998

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 10/15/2013
carol: 11/30/2011
carol: 11/29/2011
carol: 11/23/2011
wwang: 8/8/2011
terry: 8/3/2011
carol: 6/17/2011
alopez: 11/12/2010
terry: 11/10/2010
alopez: 3/2/2010
wwang: 1/6/2010
terry: 11/25/2009
wwang: 9/22/2009
terry: 9/10/2009
wwang: 8/18/2009
terry: 8/10/2009
terry: 6/3/2009
terry: 3/25/2009
carol: 5/3/2007
mgross: 1/30/2006
alopez: 12/19/2005
terry: 12/12/2005
wwang: 6/7/2005
wwang: 6/3/2005
terry: 6/2/2004
carol: 3/17/2004
tkritzer: 2/26/2004
terry: 2/25/2004
tkritzer: 9/17/2003
tkritzer: 10/18/2002
tkritzer: 10/11/2002
terry: 11/24/1999
alopez: 11/4/1999
alopez: 9/30/1999
terry: 9/29/1999
carol: 8/24/1998
terry: 8/21/1998
carol: 6/16/1998
terry: 11/6/1997
mark: 9/10/1996
terry: 8/23/1996
mark: 5/9/1996
terry: 5/2/1996
terry: 3/29/1996
mark: 2/17/1996
mark: 2/12/1996
mark: 9/22/1995
carol: 12/1/1994
terry: 7/27/1994
mimadm: 7/7/1994
jason: 6/27/1994
warfield: 3/10/1994

MIM 603919
*RECORD*
*FIELD* NO
603919
*FIELD* TI
*603919 SERINE/THREONINE PROTEIN KINASE 10; STK10
;;LOK
*FIELD* TX
Kuramochi et al. (1997) cloned the mouse gene Stk10, coding for a new
read moreserine/threonine kinase, designated LOK. Kuramochi et al. (1999)
described the cloning of a cDNA encoding the human homolog and the
detection of LOK proteins in human lymphoid cells. They deposited the
sequence of a human LOK cDNA in GenBank (GENBANK AB015718). They also
determined the chromosomal location of the gene by fluorescence in situ
hybridization: 5q35.1 in human, 11A4 in mouse, and 10q12.3 in rat. By
means of polymorphic CA repeats found in the 3-prime untranslated region
of the mouse Stk10 gene and an intersubspecific backcross mapping panel,
they mapped the Stk10 locus to a restricted region on chromosome 11
between D11Mit53 and D11Mit84. These results established STK10 as a new
marker of human chromosome 5 to define the syntenic boundary of human
chromosomes 5 and 16 on mouse chromosome 11.

*FIELD* RF
1. Kuramochi, S.; Matsuda, Y.; Okamoto, M.; Kitamura, F.; Yonekawa,
H.; Karasuyama, H.: Molecular cloning of the human gene STK10 encoding
lymphocyte-oriented kinase, and comparative chromosomal mapping of
the human, mouse, and rat homologues. Immunogenetics 49: 369-375,
1999.

2. Kuramochi, S.; Moriguchi, T.; Kuida, K.; Endo, J.; Semba, K.; Nishida,
E.; Karasuyama, H.: LOK is a novel mouse STE20-like protein kinase
that is expressed predominantly in lymphocytes. J. Biol. Chem. 272:
22679-22684, 1997.

*FIELD* CD
Victor A. McKusick: 6/17/1999

*FIELD* ED
jlewis: 06/18/1999
jlewis: 6/18/1999
jlewis: 6/17/1999

RBCC Red Blood Cell Collection

Full text data of STK10