Full text data of CAB39
CAB39
(MO25)
[Confidence: high (present in two of the MS resources)]
Calcium-binding protein 39 (MO25alpha; Protein Mo25)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Calcium-binding protein 39 (MO25alpha; Protein Mo25)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00032561
IPI00032561 Calcium binding protein 39 Calcium binding protein 39 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight
IPI00032561 Calcium binding protein 39 Calcium binding protein 39 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight
UniProt
Q9Y376
ID CAB39_HUMAN Reviewed; 341 AA.
AC Q9Y376;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Calcium-binding protein 39;
DE AltName: Full=MO25alpha;
DE AltName: Full=Protein Mo25;
GN Name=CAB39; Synonyms=MO25; ORFNames=CGI-66;
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 [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hypothalamus;
RA Jin W., Shi J., Ren S., Gu J., Fu S., Huang Q., Dong H., Yu Y., Fu G.,
RA Wang Y., Chen Z., Han Z.;
RT "A novel gene expressed in the human hypothalamus.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Duodenum;
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 [4]
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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 10-339.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-341 IN COMPLEX WITH
RP STK11/LKB1 AND STRADA, IDENTIFICATION IN A COMPLEX WITH STK11/LKB1 AND
RP STRADA, FUNCTION, AND MUTAGENESIS OF ARG-240 AND PHE-243.
RX PubMed=19892943; DOI=10.1126/science.1178377;
RA Zeqiraj E., Filippi B.M., Deak M., Alessi D.R., van Aalten D.M.;
RT "Structure of the LKB1-STRAD-MO25 complex reveals an allosteric
RT mechanism of kinase activation.";
RL Science 326:1707-1711(2009).
CC -!- FUNCTION: Component of a complex that binds and activates
CC STK11/LKB1. In the complex, required to stabilize the interaction
CC between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and
CC STK11/LKB1.
CC -!- SUBUNIT: Component of a trimeric complex composed of STK11/LKB1,
CC STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or
CC CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm
CC and stimulates its catalytic activity.
CC -!- INTERACTION:
CC Q9P289:MST4; NbExp=6; IntAct=EBI-306905, EBI-618239;
CC O95747:OXSR1; NbExp=3; IntAct=EBI-306905, EBI-620853;
CC Q15831:STK11; NbExp=4; IntAct=EBI-306905, EBI-306838;
CC O00506:STK25; NbExp=3; IntAct=EBI-306905, EBI-618295;
CC Q9UEW8:STK39; NbExp=4; IntAct=EBI-306905, EBI-2680974;
CC Q7RTN6:STRADA; NbExp=3; IntAct=EBI-306905, EBI-1109114;
CC Q9C0K7:STRADB; NbExp=5; IntAct=EBI-306905, EBI-306893;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
CC -!- SIMILARITY: Belongs to the Mo25 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF151824; AAD34061.1; -; mRNA.
DR EMBL; AF113536; AAF14873.1; -; mRNA.
DR EMBL; BC020570; AAH20570.1; -; mRNA.
DR RefSeq; NP_001124321.1; NM_001130849.1.
DR RefSeq; NP_001124322.1; NM_001130850.1.
DR RefSeq; NP_057373.1; NM_016289.3.
DR UniGene; Hs.603930; -.
DR PDB; 1UPK; X-ray; 1.85 A; A=1-341.
DR PDB; 1UPL; X-ray; 2.60 A; A/B=1-341.
DR PDB; 2WTK; X-ray; 2.65 A; A/D=1-341.
DR PDB; 3GNI; X-ray; 2.35 A; A=1-341.
DR PDB; 4FZA; X-ray; 3.15 A; A=11-334.
DR PDB; 4FZD; X-ray; 3.25 A; A=11-334.
DR PDB; 4FZF; X-ray; 3.64 A; A=11-334.
DR PDBsum; 1UPK; -.
DR PDBsum; 1UPL; -.
DR PDBsum; 2WTK; -.
DR PDBsum; 3GNI; -.
DR PDBsum; 4FZA; -.
DR PDBsum; 4FZD; -.
DR PDBsum; 4FZF; -.
DR ProteinModelPortal; Q9Y376; -.
DR SMR; Q9Y376; 2-336.
DR DIP; DIP-31316N; -.
DR IntAct; Q9Y376; 11.
DR MINT; MINT-5000103; -.
DR STRING; 9606.ENSP00000258418; -.
DR PhosphoSite; Q9Y376; -.
DR DMDM; 15214082; -.
DR PaxDb; Q9Y376; -.
DR PeptideAtlas; Q9Y376; -.
DR PRIDE; Q9Y376; -.
DR Ensembl; ENST00000258418; ENSP00000258418; ENSG00000135932.
DR Ensembl; ENST00000409788; ENSP00000386238; ENSG00000135932.
DR Ensembl; ENST00000410084; ENSP00000386642; ENSG00000135932.
DR GeneID; 51719; -.
DR KEGG; hsa:51719; -.
DR UCSC; uc002vqx.3; human.
DR CTD; 51719; -.
DR GeneCards; GC02P231577; -.
DR HGNC; HGNC:20292; CAB39.
DR HPA; CAB037112; -.
DR MIM; 612174; gene.
DR neXtProt; NX_Q9Y376; -.
DR PharmGKB; PA128394663; -.
DR eggNOG; NOG307443; -.
DR HOGENOM; HOG000234711; -.
DR HOVERGEN; HBG050757; -.
DR InParanoid; Q9Y376; -.
DR KO; K08272; -.
DR OMA; GIFWRFF; -.
DR OrthoDB; EOG7CK371; -.
DR PhylomeDB; Q9Y376; -.
DR Reactome; REACT_111102; Signal Transduction.
DR EvolutionaryTrace; Q9Y376; -.
DR GeneWiki; CAB39; -.
DR GenomeRNAi; 51719; -.
DR NextBio; 55768; -.
DR PRO; PR:Q9Y376; -.
DR ArrayExpress; Q9Y376; -.
DR Bgee; Q9Y376; -.
DR CleanEx; HS_CAB39; -.
DR Genevestigator; Q9Y376; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:UniProtKB.
DR GO; GO:0007050; P:cell cycle arrest; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR013878; Mo25.
DR PANTHER; PTHR10182; PTHR10182; 1.
DR Pfam; PF08569; Mo25; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Reference proteome.
FT CHAIN 1 341 Calcium-binding protein 39.
FT /FTId=PRO_0000209824.
FT MUTAGEN 240 240 R->A: Abolishes activation of STK11/LKB1;
FT when associated with A-243.
FT MUTAGEN 243 243 F->A: Abolishes activation of STK11/LKB1;
FT when associated with A-240.
FT HELIX 12 27
FT STRAND 29 31
FT HELIX 34 54
FT STRAND 58 61
FT HELIX 64 77
FT HELIX 79 85
FT HELIX 87 89
FT HELIX 92 106
FT HELIX 115 121
FT HELIX 125 132
FT HELIX 133 135
FT TURN 137 139
FT HELIX 140 151
FT HELIX 154 162
FT HELIX 164 167
FT HELIX 168 172
FT HELIX 178 193
FT HELIX 196 205
FT HELIX 207 217
FT HELIX 223 238
FT HELIX 240 242
FT HELIX 243 249
FT HELIX 253 262
FT HELIX 268 283
FT HELIX 289 297
FT HELIX 299 308
FT TURN 309 312
FT HELIX 314 316
FT HELIX 318 331
SQ SEQUENCE 341 AA; 39869 MW; EC710A528B6F9811 CRC64;
MPFPFGKSHK SPADIVKNLK ESMAVLEKQD ISDKKAEKAT EEVSKNLVAM KEILYGTNEK
EPQTEAVAQL AQELYNSGLL STLVADLQLI DFEGKKDVAQ IFNNILRRQI GTRTPTVEYI
CTQQNILFML LKGYESPEIA LNCGIMLREC IRHEPLAKII LWSEQFYDFF RYVEMSTFDI
ASDAFATFKD LLTRHKLLSA EFLEQHYDRF FSEYEKLLHS ENYVTKRQSL KLLGELLLDR
HNFTIMTKYI SKPENLKLMM NLLRDKSRNI QFEAFHVFKV FVANPNKTQP ILDILLKNQA
KLIEFLSKFQ NDRTEDEQFN DEKTYLVKQI RDLKRPAQQE A
//
ID CAB39_HUMAN Reviewed; 341 AA.
AC Q9Y376;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Calcium-binding protein 39;
DE AltName: Full=MO25alpha;
DE AltName: Full=Protein Mo25;
GN Name=CAB39; Synonyms=MO25; ORFNames=CGI-66;
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 [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hypothalamus;
RA Jin W., Shi J., Ren S., Gu J., Fu S., Huang Q., Dong H., Yu Y., Fu G.,
RA Wang Y., Chen Z., Han Z.;
RT "A novel gene expressed in the human hypothalamus.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Duodenum;
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 [4]
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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 10-339.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1-341 IN COMPLEX WITH
RP STK11/LKB1 AND STRADA, IDENTIFICATION IN A COMPLEX WITH STK11/LKB1 AND
RP STRADA, FUNCTION, AND MUTAGENESIS OF ARG-240 AND PHE-243.
RX PubMed=19892943; DOI=10.1126/science.1178377;
RA Zeqiraj E., Filippi B.M., Deak M., Alessi D.R., van Aalten D.M.;
RT "Structure of the LKB1-STRAD-MO25 complex reveals an allosteric
RT mechanism of kinase activation.";
RL Science 326:1707-1711(2009).
CC -!- FUNCTION: Component of a complex that binds and activates
CC STK11/LKB1. In the complex, required to stabilize the interaction
CC between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and
CC STK11/LKB1.
CC -!- SUBUNIT: Component of a trimeric complex composed of STK11/LKB1,
CC STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or
CC CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm
CC and stimulates its catalytic activity.
CC -!- INTERACTION:
CC Q9P289:MST4; NbExp=6; IntAct=EBI-306905, EBI-618239;
CC O95747:OXSR1; NbExp=3; IntAct=EBI-306905, EBI-620853;
CC Q15831:STK11; NbExp=4; IntAct=EBI-306905, EBI-306838;
CC O00506:STK25; NbExp=3; IntAct=EBI-306905, EBI-618295;
CC Q9UEW8:STK39; NbExp=4; IntAct=EBI-306905, EBI-2680974;
CC Q7RTN6:STRADA; NbExp=3; IntAct=EBI-306905, EBI-1109114;
CC Q9C0K7:STRADB; NbExp=5; IntAct=EBI-306905, EBI-306893;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
CC -!- SIMILARITY: Belongs to the Mo25 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF151824; AAD34061.1; -; mRNA.
DR EMBL; AF113536; AAF14873.1; -; mRNA.
DR EMBL; BC020570; AAH20570.1; -; mRNA.
DR RefSeq; NP_001124321.1; NM_001130849.1.
DR RefSeq; NP_001124322.1; NM_001130850.1.
DR RefSeq; NP_057373.1; NM_016289.3.
DR UniGene; Hs.603930; -.
DR PDB; 1UPK; X-ray; 1.85 A; A=1-341.
DR PDB; 1UPL; X-ray; 2.60 A; A/B=1-341.
DR PDB; 2WTK; X-ray; 2.65 A; A/D=1-341.
DR PDB; 3GNI; X-ray; 2.35 A; A=1-341.
DR PDB; 4FZA; X-ray; 3.15 A; A=11-334.
DR PDB; 4FZD; X-ray; 3.25 A; A=11-334.
DR PDB; 4FZF; X-ray; 3.64 A; A=11-334.
DR PDBsum; 1UPK; -.
DR PDBsum; 1UPL; -.
DR PDBsum; 2WTK; -.
DR PDBsum; 3GNI; -.
DR PDBsum; 4FZA; -.
DR PDBsum; 4FZD; -.
DR PDBsum; 4FZF; -.
DR ProteinModelPortal; Q9Y376; -.
DR SMR; Q9Y376; 2-336.
DR DIP; DIP-31316N; -.
DR IntAct; Q9Y376; 11.
DR MINT; MINT-5000103; -.
DR STRING; 9606.ENSP00000258418; -.
DR PhosphoSite; Q9Y376; -.
DR DMDM; 15214082; -.
DR PaxDb; Q9Y376; -.
DR PeptideAtlas; Q9Y376; -.
DR PRIDE; Q9Y376; -.
DR Ensembl; ENST00000258418; ENSP00000258418; ENSG00000135932.
DR Ensembl; ENST00000409788; ENSP00000386238; ENSG00000135932.
DR Ensembl; ENST00000410084; ENSP00000386642; ENSG00000135932.
DR GeneID; 51719; -.
DR KEGG; hsa:51719; -.
DR UCSC; uc002vqx.3; human.
DR CTD; 51719; -.
DR GeneCards; GC02P231577; -.
DR HGNC; HGNC:20292; CAB39.
DR HPA; CAB037112; -.
DR MIM; 612174; gene.
DR neXtProt; NX_Q9Y376; -.
DR PharmGKB; PA128394663; -.
DR eggNOG; NOG307443; -.
DR HOGENOM; HOG000234711; -.
DR HOVERGEN; HBG050757; -.
DR InParanoid; Q9Y376; -.
DR KO; K08272; -.
DR OMA; GIFWRFF; -.
DR OrthoDB; EOG7CK371; -.
DR PhylomeDB; Q9Y376; -.
DR Reactome; REACT_111102; Signal Transduction.
DR EvolutionaryTrace; Q9Y376; -.
DR GeneWiki; CAB39; -.
DR GenomeRNAi; 51719; -.
DR NextBio; 55768; -.
DR PRO; PR:Q9Y376; -.
DR ArrayExpress; Q9Y376; -.
DR Bgee; Q9Y376; -.
DR CleanEx; HS_CAB39; -.
DR Genevestigator; Q9Y376; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:UniProtKB.
DR GO; GO:0007050; P:cell cycle arrest; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR013878; Mo25.
DR PANTHER; PTHR10182; PTHR10182; 1.
DR Pfam; PF08569; Mo25; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Reference proteome.
FT CHAIN 1 341 Calcium-binding protein 39.
FT /FTId=PRO_0000209824.
FT MUTAGEN 240 240 R->A: Abolishes activation of STK11/LKB1;
FT when associated with A-243.
FT MUTAGEN 243 243 F->A: Abolishes activation of STK11/LKB1;
FT when associated with A-240.
FT HELIX 12 27
FT STRAND 29 31
FT HELIX 34 54
FT STRAND 58 61
FT HELIX 64 77
FT HELIX 79 85
FT HELIX 87 89
FT HELIX 92 106
FT HELIX 115 121
FT HELIX 125 132
FT HELIX 133 135
FT TURN 137 139
FT HELIX 140 151
FT HELIX 154 162
FT HELIX 164 167
FT HELIX 168 172
FT HELIX 178 193
FT HELIX 196 205
FT HELIX 207 217
FT HELIX 223 238
FT HELIX 240 242
FT HELIX 243 249
FT HELIX 253 262
FT HELIX 268 283
FT HELIX 289 297
FT HELIX 299 308
FT TURN 309 312
FT HELIX 314 316
FT HELIX 318 331
SQ SEQUENCE 341 AA; 39869 MW; EC710A528B6F9811 CRC64;
MPFPFGKSHK SPADIVKNLK ESMAVLEKQD ISDKKAEKAT EEVSKNLVAM KEILYGTNEK
EPQTEAVAQL AQELYNSGLL STLVADLQLI DFEGKKDVAQ IFNNILRRQI GTRTPTVEYI
CTQQNILFML LKGYESPEIA LNCGIMLREC IRHEPLAKII LWSEQFYDFF RYVEMSTFDI
ASDAFATFKD LLTRHKLLSA EFLEQHYDRF FSEYEKLLHS ENYVTKRQSL KLLGELLLDR
HNFTIMTKYI SKPENLKLMM NLLRDKSRNI QFEAFHVFKV FVANPNKTQP ILDILLKNQA
KLIEFLSKFQ NDRTEDEQFN DEKTYLVKQI RDLKRPAQQE A
//
MIM
612174
*RECORD*
*FIELD* NO
612174
*FIELD* TI
*612174 CALCIUM-BINDING PROTEIN 39; CAB39
;;MO25-ALPHA
*FIELD* TX
CLONING
By searching databases using peptide fragments of proteins that
read moreinteracted with the serine/threonine protein kinase LKB1 (STK11; 602216)
in HeLa cells, Boudeau et al. (2003) identified CAB39, which they
designated MO25-alpha. The deduced 341-amino acid protein shares a high
degree of conservation with its C. elegans and Drosophila orthologs.
Northern blot analysis detected a 4.2-kb MO25-alpha transcript in all
tissues examined, with highest expression in skeletal muscle. Western
blot analysis detected MO25-alpha in most tissues and cell lines
examined. Endogenous MO25-alpha in HeLa cells had an apparent molecular
mass of 40 kD by SDS-PAGE.
GENE FUNCTION
By immunoprecipitation analysis of human and rat cells, Boudeau et al.
(2003) showed that MO25-alpha associated with STRAD-alpha (608626) and
LKB1. Cotransfection and mutation analysis revealed that MO25-alpha
interacted directly with STRAD-alpha rather than with LKB1, and the
interaction required the last 3 residues of STRAD-alpha. MO25-alpha also
interacted with STRAD-beta (ALS2CR2; 607333) in a complex with LKB1.
MO25-alpha and STRAD-alpha anchored LKB1 in the cytoplasm, excluding it
from the nucleus. Moreover, MO25-alpha enhanced formation of
LKB1-STRAD-alpha complexes in vivo and stimulated LKB1 catalytic
activity about 10-fold. Boudeau et al. (2003) concluded that MO25-alpha
may function as a scaffolding component of the LKB1-STRAD complex and
regulate LKB1 activity and cellular localization.
Using mutagenesis, Boudeau et al. (2004) identified 2 binding sites on
opposite surfaces of MO25-alpha that were required for assembly of the
MO25-alpha-STRAD-alpha-LKB1 complex.
Denning et al. (2012) identified a mechanism of cell extrusion that is
caspase-independent and that can eliminate a subset of the C. elegans
cells programmed to die during embryonic development. In wildtype
animals, these cells die soon after their generation through
caspase-mediated apoptosis. However, in mutants lacking all 4 C. elegans
caspase genes, these cells were eliminated by being extruded from the
developing embryo into the extraembryonic space of the egg. The shed
cells showed apoptosis-like cytologic and morphologic characteristics,
indicating that apoptosis can occur in the absence of caspases in C.
elegans. Denning et al. (2012) described a kinase pathway required for
cell extrusion involving Par4, Strd1, and Mop25.1/25.2, the C. elegans
homologs of the mammalian tumor suppressor kinase LKB1 (602216) and its
binding partners STRAD-alpha (608626) and MO25-alpha. The AMPK-related
kinase Pig1, a possible target of the Par4-Strd1-Mop25 kinase complex,
is also required for cell shedding. Pig1 promotes shed cell detachment
by preventing the cell surface expression of cell adhesion molecules.
Denning et al. (2012) concluded that their findings revealed a mechanism
for apoptotic cell elimination that is fundamentally distinct from that
of canonical programmed cell death.
BIOCHEMICAL FEATURES
- Crystal Structure
Zeqiraj et al. (2009) described the structure of the core heterotrimeric
LKB1-STRAD-alpha-MO25-alpha complex, revealing an unusual allosteric
mechanism of LKB1 activation. STRAD-alpha adopts a closed conformation
typical of active protein kinases and binds LKB1 as a pseudosubstrate.
STRAD-alpha and MO25-alpha promote the active conformation of LKB1,
which is stabilized by MO25-alpha interacting with the LKB1 activation
loop. Zeqiraj et al. (2009) suggested that this previously undescribed
mechanism of kinase activation may be relevant to understanding the
evolution of other pseudokinases, and also commented that the structure
reveals how mutations found in Peutz-Jeghers (175200) syndrome and in
various sporadic cancers impair LKB1 function.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CAB39
gene to chromosome 2 (TMAP RH94102).
*FIELD* RF
1. Boudeau, J.; Baas, A. F.; Deak, M.; Morrice, N. A.; Kieloch, A.;
Schutkowski, M.; Prescott, A. R.; Clevers, H. C.; Alessi, D. R.:
MO25-alpha/beta interact with STRAD-alpha/beta enhancing their ability
to bind, activate and localize LKB1 in the cytoplasm. EMBO J. 22:
5102-5114, 2003.
2. Boudeau, J.; Scott, J. W.; Resta, N.; Deak, M.; Kieloch, A.; Komander,
D.; Hardie, D. G.; Prescott, A. R.; van Aalten, D. M. F.; Alessi,
D. R.: Analysis of the LKB1-STRAD-MO25 complex. J. Cell Sci. 117:
6365-6375, 2004.
3. Denning, D. P.; Hatch, V.; Horvitz, H. R.: Programmed elimination
of cells by caspase-independent cell extrusion in C. elegans. Nature 488:
226-230, 2012.
4. Zeqiraj, E.; Filippi, B. M.; Deak, M.; Alessi, D. R.; van Aalten,
D. M. F.: Structure of the LKB1-STRAD-MO25 complex reveals an allosteric
mechanism of kinase activation. Science 326: 1707-1711, 2009.
*FIELD* CN
Ada Hamosh - updated: 8/28/2012
Ada Hamosh - updated: 1/8/2010
*FIELD* CD
Patricia A. Hartz: 7/14/2008
*FIELD* ED
alopez: 08/29/2012
terry: 8/28/2012
alopez: 1/11/2010
terry: 1/8/2010
terry: 9/4/2009
mgross: 7/14/2008
*RECORD*
*FIELD* NO
612174
*FIELD* TI
*612174 CALCIUM-BINDING PROTEIN 39; CAB39
;;MO25-ALPHA
*FIELD* TX
CLONING
By searching databases using peptide fragments of proteins that
read moreinteracted with the serine/threonine protein kinase LKB1 (STK11; 602216)
in HeLa cells, Boudeau et al. (2003) identified CAB39, which they
designated MO25-alpha. The deduced 341-amino acid protein shares a high
degree of conservation with its C. elegans and Drosophila orthologs.
Northern blot analysis detected a 4.2-kb MO25-alpha transcript in all
tissues examined, with highest expression in skeletal muscle. Western
blot analysis detected MO25-alpha in most tissues and cell lines
examined. Endogenous MO25-alpha in HeLa cells had an apparent molecular
mass of 40 kD by SDS-PAGE.
GENE FUNCTION
By immunoprecipitation analysis of human and rat cells, Boudeau et al.
(2003) showed that MO25-alpha associated with STRAD-alpha (608626) and
LKB1. Cotransfection and mutation analysis revealed that MO25-alpha
interacted directly with STRAD-alpha rather than with LKB1, and the
interaction required the last 3 residues of STRAD-alpha. MO25-alpha also
interacted with STRAD-beta (ALS2CR2; 607333) in a complex with LKB1.
MO25-alpha and STRAD-alpha anchored LKB1 in the cytoplasm, excluding it
from the nucleus. Moreover, MO25-alpha enhanced formation of
LKB1-STRAD-alpha complexes in vivo and stimulated LKB1 catalytic
activity about 10-fold. Boudeau et al. (2003) concluded that MO25-alpha
may function as a scaffolding component of the LKB1-STRAD complex and
regulate LKB1 activity and cellular localization.
Using mutagenesis, Boudeau et al. (2004) identified 2 binding sites on
opposite surfaces of MO25-alpha that were required for assembly of the
MO25-alpha-STRAD-alpha-LKB1 complex.
Denning et al. (2012) identified a mechanism of cell extrusion that is
caspase-independent and that can eliminate a subset of the C. elegans
cells programmed to die during embryonic development. In wildtype
animals, these cells die soon after their generation through
caspase-mediated apoptosis. However, in mutants lacking all 4 C. elegans
caspase genes, these cells were eliminated by being extruded from the
developing embryo into the extraembryonic space of the egg. The shed
cells showed apoptosis-like cytologic and morphologic characteristics,
indicating that apoptosis can occur in the absence of caspases in C.
elegans. Denning et al. (2012) described a kinase pathway required for
cell extrusion involving Par4, Strd1, and Mop25.1/25.2, the C. elegans
homologs of the mammalian tumor suppressor kinase LKB1 (602216) and its
binding partners STRAD-alpha (608626) and MO25-alpha. The AMPK-related
kinase Pig1, a possible target of the Par4-Strd1-Mop25 kinase complex,
is also required for cell shedding. Pig1 promotes shed cell detachment
by preventing the cell surface expression of cell adhesion molecules.
Denning et al. (2012) concluded that their findings revealed a mechanism
for apoptotic cell elimination that is fundamentally distinct from that
of canonical programmed cell death.
BIOCHEMICAL FEATURES
- Crystal Structure
Zeqiraj et al. (2009) described the structure of the core heterotrimeric
LKB1-STRAD-alpha-MO25-alpha complex, revealing an unusual allosteric
mechanism of LKB1 activation. STRAD-alpha adopts a closed conformation
typical of active protein kinases and binds LKB1 as a pseudosubstrate.
STRAD-alpha and MO25-alpha promote the active conformation of LKB1,
which is stabilized by MO25-alpha interacting with the LKB1 activation
loop. Zeqiraj et al. (2009) suggested that this previously undescribed
mechanism of kinase activation may be relevant to understanding the
evolution of other pseudokinases, and also commented that the structure
reveals how mutations found in Peutz-Jeghers (175200) syndrome and in
various sporadic cancers impair LKB1 function.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CAB39
gene to chromosome 2 (TMAP RH94102).
*FIELD* RF
1. Boudeau, J.; Baas, A. F.; Deak, M.; Morrice, N. A.; Kieloch, A.;
Schutkowski, M.; Prescott, A. R.; Clevers, H. C.; Alessi, D. R.:
MO25-alpha/beta interact with STRAD-alpha/beta enhancing their ability
to bind, activate and localize LKB1 in the cytoplasm. EMBO J. 22:
5102-5114, 2003.
2. Boudeau, J.; Scott, J. W.; Resta, N.; Deak, M.; Kieloch, A.; Komander,
D.; Hardie, D. G.; Prescott, A. R.; van Aalten, D. M. F.; Alessi,
D. R.: Analysis of the LKB1-STRAD-MO25 complex. J. Cell Sci. 117:
6365-6375, 2004.
3. Denning, D. P.; Hatch, V.; Horvitz, H. R.: Programmed elimination
of cells by caspase-independent cell extrusion in C. elegans. Nature 488:
226-230, 2012.
4. Zeqiraj, E.; Filippi, B. M.; Deak, M.; Alessi, D. R.; van Aalten,
D. M. F.: Structure of the LKB1-STRAD-MO25 complex reveals an allosteric
mechanism of kinase activation. Science 326: 1707-1711, 2009.
*FIELD* CN
Ada Hamosh - updated: 8/28/2012
Ada Hamosh - updated: 1/8/2010
*FIELD* CD
Patricia A. Hartz: 7/14/2008
*FIELD* ED
alopez: 08/29/2012
terry: 8/28/2012
alopez: 1/11/2010
terry: 1/8/2010
terry: 9/4/2009
mgross: 7/14/2008