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ID STRAA_HUMAN Reviewed; 431 AA.
AC Q7RTN6; Q7Z4K9; Q8NC31; Q8NCF1; Q9H272;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-MAR-2009, entry version 49.
DE RecName: Full=STE20-related kinase adapter protein alpha;
DE Short=STRAD alpha;
DE AltName: Full=STE20-related adapter protein;
DE AltName: Full=Serologically defined breast cancer antigen NY-BR-96;
GN Name=STRADA; Synonyms=LYK5, STRAD;
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] (ISOFORM 1).
RC TISSUE=Mammary tumor;
RX MEDLINE=22633220; PubMed=12747765;
RA Scanlan M.J., Gout I., Gordon C.M., Williamson B., Stockert E.,
RA Gure A.O., Jaeger D., Chen Y.-T., Mackay A., O'Hare M.J., Old L.J.;
RT "Humoral immunity to human breast cancer: antigen definition and
RT quantitative analysis of mRNA expression.";
RL Cancer Immun. 1:4-4(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Shan Y.X., Huang C.Q., Yu L.;
RT "Cloning, characterization and localization of lyk5 gene.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Teratocarcinoma;
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 [4]
RP IDENTIFICATION (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH STK11, MUTAGENESIS OF THR-329 AND THR-419, AND
RP PHOSPHORYLATION AT THR-329 AND THR-419.
RX MEDLINE=22688956; PubMed=12805220; DOI=10.1093/emboj/cdg292;
RA Baas A.F., Boudeau J., Sapkota G.P., Smit L., Medema R., Morrice N.A.,
RA Alessi D.R., Clevers H.C.;
RT "Activation of the tumour suppressor kinase LKB1 by the STE20-like
RT pseudokinase STRAD.";
RL EMBO J. 22:3062-3072(2003).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH STK11 AND CAB39.
RX PubMed=14517248; DOI=10.1093/emboj/cdg490;
RA Boudeau J., Baas A.F., Deak M., Morrice N.A., Kieloch A.,
RA Schutkowski M., Prescott A.R., Clevers H.C., Alessi D.R.;
RT "MO25alpha/beta interact with STRADalpha/beta enhancing their ability
RT to bind, activate and localize LKB1 in the cytoplasm.";
RL EMBO J. 22:5102-5114(2003).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH CAB39.
RX PubMed=14730349; DOI=10.1038/nsmb716;
RA Milburn C.C., Boudeau J., Deak M., Alessi D.R., van Aalten D.M.;
RT "Crystal structure of MO25 alpha in complex with the C-terminus of the
RT pseudo kinase STE20-related adaptor.";
RL Nat. Struct. Mol. Biol. 11:193-200(2004).
RN [7]
RP INVOLVEMENT IN PMSE.
RX PubMed=17522105; DOI=10.1093/brain/awm100;
RA Puffenberger E.G., Strauss K.A., Ramsey K.E., Craig D.W.,
RA Stephan D.A., Robinson D.L., Hendrickson C.L., Gottlieb S.,
RA Ramsay D.A., Siu V.M., Heuer G.G., Crino P.B., Morton D.H.;
RT "Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a
RT homozygous 7-kilobase deletion in LYK5.";
RL Brain 130:1929-1941(2007).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] TRP-13; ILE-60 AND SER-64.
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: Pseudokinase which, in complex with CAB39, binds to and
CC activates STK11. Relocates STK11 from the nucleus to the
CC cytoplasm. Plays an essential role in STK11-mediated G1 cell cycle
CC arrest.
CC -!- INTERACTION:
CC Q15831:STK11; NbExp=3; IntAct=EBI-1109114, EBI-306838;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7RTN6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7RTN6-2; Sequence=VSP_052219, VSP_052220, VSP_052221;
CC Name=3;
CC IsoId=Q7RTN6-3; Sequence=VSP_052219;
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- DISEASE: Deletions involving STRADA are the cause of
CC polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome
CC (PMSE) [MIM:611087]. Affected children have large heads,
CC infantile-onset intractable multifocal seizures and severe
CC psychomotor retardation. Neuropathological studies reveal
CC megalencephaly, ventriculomegaly, cytomegaly and extensive
CC vacuolization and astrocytosis of white matter.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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DR EMBL; AF308302; AAG48269.1; -; mRNA.
DR EMBL; AY290821; AAP42280.1; -; mRNA.
DR EMBL; AK074771; BAC11197.1; -; mRNA.
DR EMBL; AK075005; BAC11349.1; -; mRNA.
DR EMBL; BK001542; DAA01797.1; -; mRNA.
DR IPI; IPI00300700; -.
DR IPI; IPI00396083; -.
DR IPI; IPI00456673; -.
DR RefSeq; NP_001003786.1; -.
DR RefSeq; NP_001003787.1; -.
DR RefSeq; NP_001003788.1; -.
DR RefSeq; NP_699166.2; -.
DR UniGene; Hs.514402; -.
DR PDB; 1UPK; X-ray; 1.85 A; B=420-431.
DR PDBsum; 1UPK; -.
DR IntAct; Q7RTN6; 1.
DR PRIDE; Q7RTN6; -.
DR Ensembl; ENSG00000125695; Homo sapiens.
DR GeneID; 92335; -.
DR KEGG; hsa:92335; -.
DR GeneCards; GC17M059134; -.
DR HGNC; HGNC:30172; STRADA.
DR MIM; 608626; gene.
DR MIM; 611087; phenotype.
DR HOVERGEN; Q7RTN6; -.
DR NextBio; 77700; -.
DR ArrayExpress; Q7RTN6; -.
DR Bgee; Q7RTN6; -.
DR GermOnline; ENSG00000125695; Homo sapiens.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005515; F:protein binding; IPI:IntAct.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein amino acid phosphorylation; IEA:InterPro.
DR GO; GO:0006611; P:protein export from nucleus; IDA:UniProtKB.
DR InterPro; IPR000719; Prot_kinase_core.
DR InterPro; IPR017442; Se/Thr_pkinase-rel.
DR Pfam; PF00069; Pkinase; 1.
DR ProDom; PD000001; Prot_kinase; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle;
KW Chromosomal rearrangement; Cytoplasm; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Transferase.
FT CHAIN 1 431 STE20-related kinase adapter protein
FT alpha.
FT /FTId=PRO_0000260035.
FT DOMAIN 69 379 Protein kinase.
FT MOD_RES 329 329 Phosphothreonine; by STK11.
FT MOD_RES 419 419 Phosphothreonine; by STK11.
FT VAR_SEQ 5 41 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_052219.
FT VAR_SEQ 368 417 PSASTLLNHSFFKQIKRRASEALPELLRPVTPITNFEGSQS
FT QDHSGIFGL -> YPCWPGPGLRESRGCSGG (in
FT isoform 2).
FT /FTId=VSP_052220.
FT VAR_SEQ 418 431 Missing (in isoform 2).
FT /FTId=VSP_052221.
FT VARIANT 13 13 R -> W.
FT /FTId=VAR_041377.
FT VARIANT 60 60 S -> I.
FT /FTId=VAR_041378.
FT VARIANT 64 64 P -> S.
FT /FTId=VAR_041379.
FT MUTAGEN 329 329 T->A: Loss of STK11-mediated
FT phosphorylation.
FT MUTAGEN 419 419 T->A: Loss of STK11-mediated
FT phosphorylation.
FT CONFLICT 339 339 S -> W (in Ref. 1; AAG48269).
FT CONFLICT 363 363 N -> H (in Ref. 3; BAC11349).
FT CONFLICT 388 388 E -> K (in Ref. 1; AAG48269).
SQ SEQUENCE 431 AA; 48369 MW; 9CC0A78D9CC6FC2C CRC64;
MSFLVSKPER IRRWVSEKFI VEGLRDLELF GEQPPGDTRR KTNDASSESI ASFSKQEVMS
SFLPEGGCYE LLTVIGKGFE DLMTVNLARY KPTGEYVTVR RINLEACSNE MVTFLQGELH
VSKLFNHPNI VPYRATFIAD NELWVVTSFM AYGSAKDLIC THFMDGMNEL AIAYILQGVL
KALDYIHHMG YVHRSVKASH ILISVDGKVY LSGLRSNLSM ISHGQRQRVV HDFPKYSVKV
LPWLSPEVLQ QNLQGYDAKS DIYSVGITAC ELANGHVPFK DMPATQMLLE KLNGTVPCLL
DTSTIPAEEL TMSPSRSVAN SGLSDSLTTS TPRPSNGDSP SHPYHRTFSP HFHHFVEQCL
QRNPDARPSA STLLNHSFFK QIKRRASEAL PELLRPVTPI TNFEGSQSQD HSGIFGLVTN
LEELEVDDWE F
//