STRAB_HUMAN
ID STRAB_HUMAN Reviewed; 418 AA.
AC Q9C0K7; Q5BKY7; Q9P1L0;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=STE20-related kinase adapter protein beta;
DE Short=STRAD beta;
DE AltName: Full=Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein;
DE AltName: Full=CALS-21;
DE AltName: Full=ILP-interacting protein;
DE AltName: Full=Pseudokinase ALS2CR2;
GN Name=STRADB; Synonyms=ALS2CR2, ILPIP; ORFNames=PRO1038;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11161814; DOI=10.1006/geno.2000.6392;
RA Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D.,
RA Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E.,
RA Hayden M.R.;
RT "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and
RT ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical
RT region at chromosome 2q33-q34: candidate genes for ALS2.";
RL Genomics 71:200-213(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND
RP INTERACTION WITH BIRC4.
RX PubMed=12048196; DOI=10.1074/jbc.m203312200;
RA Sanna M.G., Da Silva Correia J., Luo Y., Chuang B., Paulson L.M.,
RA Nguyen B., Deveraux Q.L., Ulevitch R.J.;
RT "ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated
RT activation of JNK1 and protection against apoptosis.";
RL J. Biol. Chem. 277:30454-30462(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J.,
RA Liu M., He F.;
RT "Functional prediction of the coding sequences of 121 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH STK11/LKB1 AND CAB39.
RX PubMed=14517248; DOI=10.1093/emboj/cdg490;
RA Boudeau J., Baas A.F., Deak M., Morrice N.A., Kieloch A., Schutkowski M.,
RA Prescott A.R., Clevers H.C., Alessi D.R.;
RT "MO25alpha/beta interact with STRADalpha/beta enhancing their ability to
RT bind, activate and localize LKB1 in the cytoplasm.";
RL EMBO J. 22:5102-5114(2003).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] GLU-155 AND LEU-386.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Pseudokinase which, in complex with CAB39/MO25
CC (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates
CC STK11/LKB1. Adopts a closed conformation typical of active protein
CC kinases and binds STK11/LKB1 as a pseudosubstrate, promoting
CC conformational change of STK11/LKB1 in an active conformation (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:14517248}.
CC -!- SUBUNIT: Component of a trimeric complex composed of STK11/LKB1, STRAD
CC (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta):
CC the complex tethers STK11/LKB1 in the cytoplasm and stimulates its
CC catalytic activity. Interacts with BIRC4/XIAP. These two proteins are
CC likely to coexist in a complex with TAK1, TRAF6, TAB1 and TAB2.
CC {ECO:0000269|PubMed:12048196, ECO:0000269|PubMed:14517248}.
CC -!- INTERACTION:
CC Q9C0K7; Q9Y376: CAB39; NbExp=6; IntAct=EBI-306893, EBI-306905;
CC Q9C0K7; Q15831: STK11; NbExp=8; IntAct=EBI-306893, EBI-306838;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14517248}. Cytoplasm
CC {ECO:0000269|PubMed:14517248}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=ILPIP-alpha;
CC IsoId=Q9C0K7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9C0K7-2; Sequence=VSP_016623, VSP_016624;
CC Name=3; Synonyms=ILPIP-beta;
CC IsoId=Q9C0K7-3; Sequence=VSP_016625;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, testis,
CC liver and colon. {ECO:0000269|PubMed:11161814,
CC ECO:0000269|PubMed:12048196}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- CAUTION: Ser-184 is present instead of the conserved Asp which is
CC expected to be an active site residue. {ECO:0000305}.
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DR EMBL; AB038950; BAB32500.1; -; mRNA.
DR EMBL; AY093697; AAM19143.1; -; mRNA.
DR EMBL; AF116618; AAF71042.1; -; mRNA.
DR EMBL; AK027637; BAB55254.1; -; mRNA.
DR EMBL; AC007282; AAY14692.1; -; Genomic_DNA.
DR EMBL; BC008302; AAH08302.1; -; mRNA.
DR EMBL; BC090871; AAH90871.1; -; mRNA.
DR CCDS; CCDS2348.1; -. [Q9C0K7-1]
DR CCDS; CCDS56161.1; -. [Q9C0K7-2]
DR RefSeq; NP_001193793.1; NM_001206864.1. [Q9C0K7-2]
DR RefSeq; NP_061041.2; NM_018571.5. [Q9C0K7-1]
DR RefSeq; XP_016859927.1; XM_017004438.1. [Q9C0K7-3]
DR AlphaFoldDB; Q9C0K7; -.
DR SMR; Q9C0K7; -.
DR BioGRID; 120668; 21.
DR ComplexPortal; CPX-2868; LKB1-STRAD-MO25 serine/threonine protein kinase complex, CAB39-STRADB variant.
DR ComplexPortal; CPX-2869; LKB1-STRAD-MO25 serine/threonine protein kinase complex, CAB39L-STRADB variant.
DR IntAct; Q9C0K7; 23.
DR MINT; Q9C0K7; -.
DR STRING; 9606.ENSP00000194530; -.
DR ChEMBL; CHEMBL4105756; -.
DR iPTMnet; Q9C0K7; -.
DR PhosphoSitePlus; Q9C0K7; -.
DR BioMuta; STRADB; -.
DR DMDM; 74762722; -.
DR EPD; Q9C0K7; -.
DR jPOST; Q9C0K7; -.
DR MassIVE; Q9C0K7; -.
DR PaxDb; Q9C0K7; -.
DR PeptideAtlas; Q9C0K7; -.
DR PRIDE; Q9C0K7; -.
DR ProteomicsDB; 80073; -. [Q9C0K7-1]
DR ProteomicsDB; 80074; -. [Q9C0K7-2]
DR ProteomicsDB; 80075; -. [Q9C0K7-3]
DR Antibodypedia; 19937; 398 antibodies from 39 providers.
DR DNASU; 55437; -.
DR Ensembl; ENST00000194530.8; ENSP00000194530.3; ENSG00000082146.13. [Q9C0K7-1]
DR Ensembl; ENST00000392249.6; ENSP00000376080.2; ENSG00000082146.13. [Q9C0K7-2]
DR GeneID; 55437; -.
DR KEGG; hsa:55437; -.
DR MANE-Select; ENST00000194530.8; ENSP00000194530.3; NM_018571.6; NP_061041.2.
DR UCSC; uc002uyd.5; human. [Q9C0K7-1]
DR CTD; 55437; -.
DR DisGeNET; 55437; -.
DR GeneCards; STRADB; -.
DR HGNC; HGNC:13205; STRADB.
DR HPA; ENSG00000082146; Low tissue specificity.
DR MIM; 607333; gene.
DR neXtProt; NX_Q9C0K7; -.
DR OpenTargets; ENSG00000082146; -.
DR PharmGKB; PA24743; -.
DR VEuPathDB; HostDB:ENSG00000082146; -.
DR eggNOG; KOG0582; Eukaryota.
DR GeneTree; ENSGT00940000155390; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q9C0K7; -.
DR OMA; TYCPWDI; -.
DR PhylomeDB; Q9C0K7; -.
DR TreeFam; TF319817; -.
DR PathwayCommons; Q9C0K7; -.
DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR SignaLink; Q9C0K7; -.
DR BioGRID-ORCS; 55437; 46 hits in 1046 CRISPR screens.
DR ChiTaRS; STRADB; human.
DR GeneWiki; ALS2CR2; -.
DR GenomeRNAi; 55437; -.
DR Pharos; Q9C0K7; Tbio.
DR PRO; PR:Q9C0K7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9C0K7; protein.
DR Bgee; ENSG00000082146; Expressed in adrenal tissue and 95 other tissues.
DR ExpressionAtlas; Q9C0K7; baseline and differential.
DR Genevisible; Q9C0K7; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1902554; C:serine/threonine protein kinase complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IBA:GO_Central.
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:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0006611; P:protein export from nucleus; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell cycle; Cytoplasm;
KW Nucleotide-binding; Nucleus; Reference proteome.
FT CHAIN 1..418
FT /note="STE20-related kinase adapter protein beta"
FT /id="PRO_0000085617"
FT DOMAIN 58..369
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 64..72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..138
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12048196, ECO:0000303|Ref.3"
FT /id="VSP_016625"
FT VAR_SEQ 372..377
FT /note="MKEESQ -> PYFEFL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016623"
FT VAR_SEQ 378..418
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016624"
FT VARIANT 155
FT /note="G -> E (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041335"
FT VARIANT 386
FT /note="P -> L (in dbSNP:rs35636836)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041336"
SQ SEQUENCE 418 AA; 47026 MW; A63ED6CCE1E18C96 CRC64;
MSLLDCFCTS RTQVESLRPE KQSETSIHQY LVDEPTLSWS RPSTRASEVL CSTNVSHYEL
QVEIGRGFDN LTSVHLARHT PTGTLVTIKI TNLENCNEER LKALQKAVIL SHFFRHPNIT
TYWTVFTVGS WLWVISPFMA YGSASQLLRT YFPEGMSETL IRNILFGAVR GLNYLHQNGC
IHRSIKASHI LISGDGLVTL SGLSHLHSLV KHGQRHRAVY DFPQFSTSVQ PWLSPELLRQ
DLHGYNVKSD IYSVGITACE LASGQVPFQD MHRTQMLLQK LKGPPYSPLD ISIFPQSESR
MKNSQSGVDS GIGESVLVSS GTHTVNSDRL HTPSSKTFSP AFFSLVQLCL QQDPEKRPSA
SSLLSHVFFK QMKEESQDSI LSLLPPAYNK PSISLPPVLP WTEPECDFPD EKDSYWEF
