Full text data of IGBP1
IGBP1
(IBP1)
[Confidence: low (only semi-automatic identification from reviews)]
Immunoglobulin-binding protein 1 (B-cell signal transduction molecule alpha 4; Protein alpha-4; CD79a-binding protein 1; Protein phosphatase 2/4/6 regulatory subunit; Renal carcinoma antigen NY-REN-16)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Immunoglobulin-binding protein 1 (B-cell signal transduction molecule alpha 4; Protein alpha-4; CD79a-binding protein 1; Protein phosphatase 2/4/6 regulatory subunit; Renal carcinoma antigen NY-REN-16)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P78318
ID IGBP1_HUMAN Reviewed; 339 AA.
AC P78318; Q8TAB2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1997, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Immunoglobulin-binding protein 1;
DE AltName: Full=B-cell signal transduction molecule alpha 4;
DE Short=Protein alpha-4;
DE AltName: Full=CD79a-binding protein 1;
DE AltName: Full=Protein phosphatase 2/4/6 regulatory subunit;
DE AltName: Full=Renal carcinoma antigen NY-REN-16;
GN Name=IGBP1; Synonyms=IBP1;
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].
RC TISSUE=B-cell;
RX PubMed=9441740; DOI=10.1006/geno.1997.5048;
RA Onda M., Inui S., Maeda K., Suzuki M., Takahashi E., Sakaguchi N.;
RT "Expression and chromosomal localization of the human alpha 4/IGBP1
RT gene, the structure of which is closely related to the yeast TAP42
RT protein of the rapamycin-sensitive signal transduction pathway.";
RL Genomics 46:373-378(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH SERINE/THREONINE PROTEIN PHOSPHATASES.
RX PubMed=9647778; DOI=10.1006/bbrc.1998.8792;
RA Chen J., Peterson R.T., Schreiber S.L.;
RT "Alpha 4 associates with protein phosphatases 2A, 4, and 6.";
RL Biochem. Biophys. Res. Commun. 247:827-832(1998).
RN [6]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [7]
RP INTERACTION WITH MID1 AND MID2.
RX PubMed=11806752; DOI=10.1186/1471-2121-3-1;
RA Short K.M., Hopwood B., Yi Z., Cox T.C.;
RT "MID1 and MID2 homo- and heterodimerise to tether the rapamycin-
RT sensitive PP2A regulatory subunit, Alpha 4, to microtubules:
RT implications for the clinical variability of X-linked Opitz GBBB
RT syndrome and other developmental disorders.";
RL BMC Cell Biol. 3:1-1(2002).
RN [8]
RP INVOLVEMENT IN MRXS28.
RX PubMed=14556245; DOI=10.1002/ajmg.a.20504;
RA Graham J.M. Jr., Wheeler P., Tackels-Horne D., Lin A.E., Hall B.D.,
RA May M., Short K.M., Schwartz C.E., Cox T.C.;
RT "A new X-linked syndrome with agenesis of the corpus callosum, mental
RT retardation, coloboma, micrognathia, and a mutation in the alpha 4
RT gene at Xq13.";
RL Am. J. Med. Genet. A 123:37-44(2003).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [10]
RP FUNCTION, AND INTERACTION WITH PPP2CA.
RX PubMed=19818709; DOI=10.1016/j.molcel.2009.09.025;
RA Kong M., Ditsworth D., Lindsten T., Thompson C.B.;
RT "Alpha4 is an essential regulator of PP2A phosphatase activity.";
RL Mol. Cell 36:51-60(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-241, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP UBIQUITINATION, AND INTERACTION WITH PPP2CA AND UBIQUITIN.
RX PubMed=20092282; DOI=10.1021/bi901837h;
RA McConnell J.L., Watkins G.R., Soss S.E., Franz H.S., McCorvey L.R.,
RA Spiller B.W., Chazin W.J., Wadzinski B.E.;
RT "Alpha4 is a ubiquitin-binding protein that regulates protein
RT serine/threonine phosphatase 2A ubiquitination.";
RL Biochemistry 49:1713-1718(2010).
RN [13]
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 [14]
RP UBIQUITINATION BY MID1, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=22613722; DOI=10.1074/jbc.M112.368613;
RA Watkins G.R., Wang N., Mazalouskas M.D., Gomez R.J., Guthrie C.R.,
RA Kraemer B.C., Schweiger S., Spiller B.W., Wadzinski B.E.;
RT "Monoubiquitination promotes calpain cleavage of the protein
RT phosphatase 2A (PP2A) regulatory subunit alpha4, altering PP2A
RT stability and microtubule-associated protein phosphorylation.";
RL J. Biol. Chem. 287:24207-24215(2012).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-234 IN COMPLEX WITH PPP2CA,
RP FUNCTION, MUTAGENESIS OF ARG-155; LYS-158; TYR-162 AND GLU-214, AND
RP INTERACTION WITH PPP2CA.
RX PubMed=23591866; DOI=10.1038/ncomms2663;
RA Jiang L., Stanevich V., Satyshur K.A., Kong M., Watkins G.R.,
RA Wadzinski B.E., Sengupta R., Xing Y.;
RT "Structural basis of protein phosphatase 2A stable latency.";
RL Nat. Commun. 4:1699-1699(2013).
CC -!- FUNCTION: Associated to surface IgM-receptor; may be involved in
CC signal transduction. Involved in regulation of the catalytic
CC activity of the phosphatases PP2A, PP4 and PP6 by protecting their
CC partially folded catalytic subunits from degradative
CC polyubiquitination until they associate with regulatory subunits.
CC -!- SUBUNIT: Interacts with partially folded PPP2CA, but not with the
CC fully active protein. Interacts with PPP2CB, and with PP4 and PP6.
CC Interacts with MID1 and MID2. Interacts with ubiquitin.
CC -!- INTERACTION:
CC P67775:PPP2CA; NbExp=10; IntAct=EBI-1055954, EBI-712311;
CC P62714:PPP2CB; NbExp=3; IntAct=EBI-1055954, EBI-1044367;
CC P60510:PPP4C; NbExp=7; IntAct=EBI-1055954, EBI-1046072;
CC O00743:PPP6C; NbExp=10; IntAct=EBI-1055954, EBI-359751;
CC O75663:TIPRL; NbExp=2; IntAct=EBI-1055954, EBI-1054735;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC heart, skeletal muscle and pancreas.
CC -!- DOMAIN: The UIM domain is required for protective effect on PP2A
CC (By similarity).
CC -!- PTM: Phosphorylated (By similarity).
CC -!- PTM: Monoubiquitination by MID1 triggers calpain-mediated cleavage
CC and switches IGBP1 activity from protective to destructive.
CC -!- DISEASE: Mental retardation, X-linked, syndromic, 28 (MRXS28)
CC [MIM:300472]: A mental retardation syndrome characterized by
CC agenesis of the corpus callosum, coloboma of the iris and optic
CC nerve, severe retrognathia, and intellectual deficit. Mental
CC retardation is defined by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the IGBP1/TAP42 family.
CC -!- SIMILARITY: Contains 1 UIM (ubiquitin-interacting motif) repeat.
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DR EMBL; Y08915; CAA70119.1; -; mRNA.
DR EMBL; BT006736; AAP35382.1; -; mRNA.
DR EMBL; AL158141; CAD13488.2; -; Genomic_DNA.
DR EMBL; AL139111; CAD13488.2; JOINED; Genomic_DNA.
DR EMBL; BC004137; AAH04137.1; -; mRNA.
DR RefSeq; NP_001542.1; NM_001551.2.
DR UniGene; Hs.496267; -.
DR PDB; 4IYP; X-ray; 2.80 A; A=1-234.
DR PDBsum; 4IYP; -.
DR ProteinModelPortal; P78318; -.
DR SMR; P78318; 1-221.
DR IntAct; P78318; 20.
DR MINT; MINT-3022988; -.
DR STRING; 9606.ENSP00000348784; -.
DR PhosphoSite; P78318; -.
DR DMDM; 14285501; -.
DR PaxDb; P78318; -.
DR PeptideAtlas; P78318; -.
DR PRIDE; P78318; -.
DR DNASU; 3476; -.
DR Ensembl; ENST00000342206; ENSP00000363661; ENSG00000089289.
DR Ensembl; ENST00000356413; ENSP00000348784; ENSG00000089289.
DR GeneID; 3476; -.
DR KEGG; hsa:3476; -.
DR UCSC; uc004dxv.3; human.
DR CTD; 3476; -.
DR GeneCards; GC0XP069353; -.
DR HGNC; HGNC:5461; IGBP1.
DR HPA; HPA000634; -.
DR HPA; HPA001004; -.
DR MIM; 300139; gene.
DR MIM; 300472; phenotype.
DR neXtProt; NX_P78318; -.
DR Orphanet; 52055; Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia.
DR PharmGKB; PA29694; -.
DR eggNOG; NOG332001; -.
DR HOGENOM; HOG000038526; -.
DR HOVERGEN; HBG052090; -.
DR InParanoid; P78318; -.
DR KO; K17606; -.
DR OMA; GSRIIQD; -.
DR OrthoDB; EOG7992R2; -.
DR PhylomeDB; P78318; -.
DR ChiTaRS; IGBP1; human.
DR GeneWiki; IGBP1; -.
DR GenomeRNAi; 3476; -.
DR NextBio; 13672; -.
DR PRO; PR:P78318; -.
DR Bgee; P78318; -.
DR CleanEx; HS_IGBP1; -.
DR Genevestigator; P78318; -.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; IDA:UniProtKB.
DR GO; GO:0042113; P:B cell activation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0035306; P:positive regulation of dephosphorylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0060632; P:regulation of microtubule-based movement; IMP:UniProtKB.
DR GO; GO:0070555; P:response to interleukin-1; IMP:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR InterPro; IPR007304; TAP42-like.
DR PANTHER; PTHR10933; PTHR10933; 1.
DR Pfam; PF04177; TAP42; 1.
DR PROSITE; PS50330; UIM; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; B-cell activation; Chaperone;
KW Complete proteome; Cytoplasm; Mental retardation; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 339 Immunoglobulin-binding protein 1.
FT /FTId=PRO_0000218618.
FT REPEAT 46 60 UIM.
FT REGION 98 202 Interaction with PPP2CA.
FT REGION 225 290 Interaction with MID1.
FT SITE 255 256 Cleavage; by calpain.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 241 241 N6-acetyllysine.
FT VARIANT 20 20 R -> K (in dbSNP:rs6625580).
FT /FTId=VAR_049570.
FT MUTAGEN 155 155 R->E: Abolishes interaction with PPP2CA.
FT MUTAGEN 158 158 K->D: Abolishes interaction with PPP2CA.
FT MUTAGEN 162 162 Y->D: Abolishes interaction with PPP2CA.
FT MUTAGEN 214 214 E->R: Abolishes interaction with PPP2CA.
FT HELIX 2 5
FT HELIX 12 27
FT HELIX 36 59
FT HELIX 68 70
FT TURN 73 75
FT HELIX 76 80
FT HELIX 81 90
FT HELIX 95 97
FT HELIX 98 118
FT STRAND 143 145
FT HELIX 156 180
FT HELIX 186 219
SQ SEQUENCE 339 AA; 39222 MW; BB00A116EB45273A CRC64;
MAAEDELQLP RLPELFETGR QLLDEVEVAT EPAGSRIVQE KVFKGLDLLE KAAEMLSQLD
LFSRNEDLEE IASTDLKYLL VPAFQGALTM KQVNPSKRLD HLQRAREHFI NYLTQCHCYH
VAEFELPKTM NNSAENHTAN SSMAYPSLVA MASQRQAKIQ RYKQKKELEH RLSAMKSAVE
SGQADDERVR EYYLLHLQRW IDISLEEIES IDQEIKILRE RDSSREASTS NSSRQERPPV
KPFILTRNMA QAKVFGAGYP SLPTMTVSDW YEQHRKYGAL PDQGIAKAAP EEFRKAAQQQ
EEQEEKEEED DEQTLHRARE WDDWKDTHPR GYGNRQNMG
//
ID IGBP1_HUMAN Reviewed; 339 AA.
AC P78318; Q8TAB2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1997, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Immunoglobulin-binding protein 1;
DE AltName: Full=B-cell signal transduction molecule alpha 4;
DE Short=Protein alpha-4;
DE AltName: Full=CD79a-binding protein 1;
DE AltName: Full=Protein phosphatase 2/4/6 regulatory subunit;
DE AltName: Full=Renal carcinoma antigen NY-REN-16;
GN Name=IGBP1; Synonyms=IBP1;
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].
RC TISSUE=B-cell;
RX PubMed=9441740; DOI=10.1006/geno.1997.5048;
RA Onda M., Inui S., Maeda K., Suzuki M., Takahashi E., Sakaguchi N.;
RT "Expression and chromosomal localization of the human alpha 4/IGBP1
RT gene, the structure of which is closely related to the yeast TAP42
RT protein of the rapamycin-sensitive signal transduction pathway.";
RL Genomics 46:373-378(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH SERINE/THREONINE PROTEIN PHOSPHATASES.
RX PubMed=9647778; DOI=10.1006/bbrc.1998.8792;
RA Chen J., Peterson R.T., Schreiber S.L.;
RT "Alpha 4 associates with protein phosphatases 2A, 4, and 6.";
RL Biochem. Biophys. Res. Commun. 247:827-832(1998).
RN [6]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [7]
RP INTERACTION WITH MID1 AND MID2.
RX PubMed=11806752; DOI=10.1186/1471-2121-3-1;
RA Short K.M., Hopwood B., Yi Z., Cox T.C.;
RT "MID1 and MID2 homo- and heterodimerise to tether the rapamycin-
RT sensitive PP2A regulatory subunit, Alpha 4, to microtubules:
RT implications for the clinical variability of X-linked Opitz GBBB
RT syndrome and other developmental disorders.";
RL BMC Cell Biol. 3:1-1(2002).
RN [8]
RP INVOLVEMENT IN MRXS28.
RX PubMed=14556245; DOI=10.1002/ajmg.a.20504;
RA Graham J.M. Jr., Wheeler P., Tackels-Horne D., Lin A.E., Hall B.D.,
RA May M., Short K.M., Schwartz C.E., Cox T.C.;
RT "A new X-linked syndrome with agenesis of the corpus callosum, mental
RT retardation, coloboma, micrognathia, and a mutation in the alpha 4
RT gene at Xq13.";
RL Am. J. Med. Genet. A 123:37-44(2003).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [10]
RP FUNCTION, AND INTERACTION WITH PPP2CA.
RX PubMed=19818709; DOI=10.1016/j.molcel.2009.09.025;
RA Kong M., Ditsworth D., Lindsten T., Thompson C.B.;
RT "Alpha4 is an essential regulator of PP2A phosphatase activity.";
RL Mol. Cell 36:51-60(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-241, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP UBIQUITINATION, AND INTERACTION WITH PPP2CA AND UBIQUITIN.
RX PubMed=20092282; DOI=10.1021/bi901837h;
RA McConnell J.L., Watkins G.R., Soss S.E., Franz H.S., McCorvey L.R.,
RA Spiller B.W., Chazin W.J., Wadzinski B.E.;
RT "Alpha4 is a ubiquitin-binding protein that regulates protein
RT serine/threonine phosphatase 2A ubiquitination.";
RL Biochemistry 49:1713-1718(2010).
RN [13]
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 [14]
RP UBIQUITINATION BY MID1, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=22613722; DOI=10.1074/jbc.M112.368613;
RA Watkins G.R., Wang N., Mazalouskas M.D., Gomez R.J., Guthrie C.R.,
RA Kraemer B.C., Schweiger S., Spiller B.W., Wadzinski B.E.;
RT "Monoubiquitination promotes calpain cleavage of the protein
RT phosphatase 2A (PP2A) regulatory subunit alpha4, altering PP2A
RT stability and microtubule-associated protein phosphorylation.";
RL J. Biol. Chem. 287:24207-24215(2012).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-234 IN COMPLEX WITH PPP2CA,
RP FUNCTION, MUTAGENESIS OF ARG-155; LYS-158; TYR-162 AND GLU-214, AND
RP INTERACTION WITH PPP2CA.
RX PubMed=23591866; DOI=10.1038/ncomms2663;
RA Jiang L., Stanevich V., Satyshur K.A., Kong M., Watkins G.R.,
RA Wadzinski B.E., Sengupta R., Xing Y.;
RT "Structural basis of protein phosphatase 2A stable latency.";
RL Nat. Commun. 4:1699-1699(2013).
CC -!- FUNCTION: Associated to surface IgM-receptor; may be involved in
CC signal transduction. Involved in regulation of the catalytic
CC activity of the phosphatases PP2A, PP4 and PP6 by protecting their
CC partially folded catalytic subunits from degradative
CC polyubiquitination until they associate with regulatory subunits.
CC -!- SUBUNIT: Interacts with partially folded PPP2CA, but not with the
CC fully active protein. Interacts with PPP2CB, and with PP4 and PP6.
CC Interacts with MID1 and MID2. Interacts with ubiquitin.
CC -!- INTERACTION:
CC P67775:PPP2CA; NbExp=10; IntAct=EBI-1055954, EBI-712311;
CC P62714:PPP2CB; NbExp=3; IntAct=EBI-1055954, EBI-1044367;
CC P60510:PPP4C; NbExp=7; IntAct=EBI-1055954, EBI-1046072;
CC O00743:PPP6C; NbExp=10; IntAct=EBI-1055954, EBI-359751;
CC O75663:TIPRL; NbExp=2; IntAct=EBI-1055954, EBI-1054735;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC heart, skeletal muscle and pancreas.
CC -!- DOMAIN: The UIM domain is required for protective effect on PP2A
CC (By similarity).
CC -!- PTM: Phosphorylated (By similarity).
CC -!- PTM: Monoubiquitination by MID1 triggers calpain-mediated cleavage
CC and switches IGBP1 activity from protective to destructive.
CC -!- DISEASE: Mental retardation, X-linked, syndromic, 28 (MRXS28)
CC [MIM:300472]: A mental retardation syndrome characterized by
CC agenesis of the corpus callosum, coloboma of the iris and optic
CC nerve, severe retrognathia, and intellectual deficit. Mental
CC retardation is defined by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the IGBP1/TAP42 family.
CC -!- SIMILARITY: Contains 1 UIM (ubiquitin-interacting motif) repeat.
CC -----------------------------------------------------------------------
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DR EMBL; Y08915; CAA70119.1; -; mRNA.
DR EMBL; BT006736; AAP35382.1; -; mRNA.
DR EMBL; AL158141; CAD13488.2; -; Genomic_DNA.
DR EMBL; AL139111; CAD13488.2; JOINED; Genomic_DNA.
DR EMBL; BC004137; AAH04137.1; -; mRNA.
DR RefSeq; NP_001542.1; NM_001551.2.
DR UniGene; Hs.496267; -.
DR PDB; 4IYP; X-ray; 2.80 A; A=1-234.
DR PDBsum; 4IYP; -.
DR ProteinModelPortal; P78318; -.
DR SMR; P78318; 1-221.
DR IntAct; P78318; 20.
DR MINT; MINT-3022988; -.
DR STRING; 9606.ENSP00000348784; -.
DR PhosphoSite; P78318; -.
DR DMDM; 14285501; -.
DR PaxDb; P78318; -.
DR PeptideAtlas; P78318; -.
DR PRIDE; P78318; -.
DR DNASU; 3476; -.
DR Ensembl; ENST00000342206; ENSP00000363661; ENSG00000089289.
DR Ensembl; ENST00000356413; ENSP00000348784; ENSG00000089289.
DR GeneID; 3476; -.
DR KEGG; hsa:3476; -.
DR UCSC; uc004dxv.3; human.
DR CTD; 3476; -.
DR GeneCards; GC0XP069353; -.
DR HGNC; HGNC:5461; IGBP1.
DR HPA; HPA000634; -.
DR HPA; HPA001004; -.
DR MIM; 300139; gene.
DR MIM; 300472; phenotype.
DR neXtProt; NX_P78318; -.
DR Orphanet; 52055; Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia.
DR PharmGKB; PA29694; -.
DR eggNOG; NOG332001; -.
DR HOGENOM; HOG000038526; -.
DR HOVERGEN; HBG052090; -.
DR InParanoid; P78318; -.
DR KO; K17606; -.
DR OMA; GSRIIQD; -.
DR OrthoDB; EOG7992R2; -.
DR PhylomeDB; P78318; -.
DR ChiTaRS; IGBP1; human.
DR GeneWiki; IGBP1; -.
DR GenomeRNAi; 3476; -.
DR NextBio; 13672; -.
DR PRO; PR:P78318; -.
DR Bgee; P78318; -.
DR CleanEx; HS_IGBP1; -.
DR Genevestigator; P78318; -.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; IDA:UniProtKB.
DR GO; GO:0042113; P:B cell activation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0035306; P:positive regulation of dephosphorylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0060632; P:regulation of microtubule-based movement; IMP:UniProtKB.
DR GO; GO:0070555; P:response to interleukin-1; IMP:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR InterPro; IPR007304; TAP42-like.
DR PANTHER; PTHR10933; PTHR10933; 1.
DR Pfam; PF04177; TAP42; 1.
DR PROSITE; PS50330; UIM; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; B-cell activation; Chaperone;
KW Complete proteome; Cytoplasm; Mental retardation; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 339 Immunoglobulin-binding protein 1.
FT /FTId=PRO_0000218618.
FT REPEAT 46 60 UIM.
FT REGION 98 202 Interaction with PPP2CA.
FT REGION 225 290 Interaction with MID1.
FT SITE 255 256 Cleavage; by calpain.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 241 241 N6-acetyllysine.
FT VARIANT 20 20 R -> K (in dbSNP:rs6625580).
FT /FTId=VAR_049570.
FT MUTAGEN 155 155 R->E: Abolishes interaction with PPP2CA.
FT MUTAGEN 158 158 K->D: Abolishes interaction with PPP2CA.
FT MUTAGEN 162 162 Y->D: Abolishes interaction with PPP2CA.
FT MUTAGEN 214 214 E->R: Abolishes interaction with PPP2CA.
FT HELIX 2 5
FT HELIX 12 27
FT HELIX 36 59
FT HELIX 68 70
FT TURN 73 75
FT HELIX 76 80
FT HELIX 81 90
FT HELIX 95 97
FT HELIX 98 118
FT STRAND 143 145
FT HELIX 156 180
FT HELIX 186 219
SQ SEQUENCE 339 AA; 39222 MW; BB00A116EB45273A CRC64;
MAAEDELQLP RLPELFETGR QLLDEVEVAT EPAGSRIVQE KVFKGLDLLE KAAEMLSQLD
LFSRNEDLEE IASTDLKYLL VPAFQGALTM KQVNPSKRLD HLQRAREHFI NYLTQCHCYH
VAEFELPKTM NNSAENHTAN SSMAYPSLVA MASQRQAKIQ RYKQKKELEH RLSAMKSAVE
SGQADDERVR EYYLLHLQRW IDISLEEIES IDQEIKILRE RDSSREASTS NSSRQERPPV
KPFILTRNMA QAKVFGAGYP SLPTMTVSDW YEQHRKYGAL PDQGIAKAAP EEFRKAAQQQ
EEQEEKEEED DEQTLHRARE WDDWKDTHPR GYGNRQNMG
//
MIM
300139
*RECORD*
*FIELD* NO
300139
*FIELD* TI
*300139 IMMUNOGLOBULIN-BINDING PROTEIN 1; IGBP1
;;PROTEIN PHOSPHATASE 2A, REGULATORY SUBUNIT ALPHA-4;;
read moreALPHA-4
*FIELD* TX
CLONING
The proliferation and differentiation of B cells is dependent upon a
B-cell antigen receptor (BCR) complex. Binding of antigens to specific
B-cell receptors results in a tyrosine phosphorylation reaction through
the BCR complex and leads to multiple signal transduction pathways. The
murine Igbp1 gene encodes a protein that coprecipitates with the MB1
(112205) protein of the BCR complex and has a possible SH3-binding motif
and multiple sites that are phosphorylated by protein kinase C under
phorbol myristate acetate activation (Inui et al., 1995). TAP42, a yeast
gene similar to Igbp1, is associated with phosphatase 2A or Sit4, all of
which are critical for the survival of yeast cells in the
rapamycin-sensitive signal transduction pathways (Di Como and Arndt,
1996). Onda et al. (1997) demonstrated the existence of an
Igbp1/TAP42-related gene in humans by Southern blot analysis with the
mouse Igbp1 cDNA probe on a DNA zoo blot. They used the mouse probe to
isolate 2 overlapping cDNA clones from a human B-cell line. The IGBP1
cDNA encodes a potential polypeptide of 339 amino acids with 82.9% amino
acid sequence homology to mouse Igbp1. This putative protein contains 4
potential N-glycosylation sites, 2 myristylation sites, 6 possible
phosphorylation sites with protein kinase C and 7 with casein kinase II,
and an amino acid stretch related to the SH3-binding consensus sequence
in a similar position to that found in mouse Igbp1 and yeast TAP42. By
Northern blot analysis, Onda et al. (1997) detected ubiquitous
expression of IGBP1 as a 1.4-kb mRNA, with highest levels of expression
found in heart, skeletal muscle, and pancreas. Antibodies against an
IGBP1 fusion protein detected a single band of 45 kD in Western blots
from human lymphoid cell lines.
GENE FUNCTION
Wildtype Mid1 (300552) colocalizes predominantly with microtubules, in
contrast to mutant versions of Mid1 found in Opitz syndrome (300000)
patients that appear clustered in the cytosol. Using yeast 2-hybrid
screening, Liu et al. (2001) found that the alpha-4 subunit of protein
phosphatases-2A, -4, and -6 bound Mid1. Localization of Mid1 and the
alpha-4 subunit was influenced by one another in transiently transfected
cells. Mid1 could recruit the alpha-4 subunit onto microtubules, and
high levels of the alpha-4 subunit could displace Mid1 into the cytosol.
Metabolic (32)P labeling of cells revealed Mid1 to be a phosphoprotein,
and coexpression of the full-length alpha-4 subunit decreased Mid1
phosphorylation, indicative of a functional interaction. Association of
GFP-Mid1 with microtubules in living cells was perturbed by inhibitors
of MAP kinase activation. Liu et al. (2001) concluded that Mid1
association with microtubules, which seems important for normal midline
development, is regulated by dynamic phosphorylation involving MAP
kinase and protein phosphatase that is targeted specifically to Mid1 by
the alpha-4 subunit.
Kong et al. (2004) demonstrated that alpha-4 is required to repress
apoptosis in mouse cells. Alpha-4 is a nonredundant regulator of the
dephosphorylation of the transcription factors c-Jun and p53 (191170).
As a result of alpha-4 deletion, multiple proapoptotic genes were
transcribed. Either inhibition of new protein synthesis or Bcl-x(L)
expression suppressed apoptosis initiated by alpha-4 deletion. Kong et
al. (2004) concluded that mammalian cell viability depends on repression
of transcription-initiated apoptosis mediated by a component of PP2A.
MAPPING
By fluorescence in situ hybridization, Onda et al. (1997) isolated a
genomic human BAC clone of IGBP1 and mapped the gene to chromosome
Xq13.1-13.3.
MOLECULAR GENETICS
In 2 brothers with agenesis of the corpus callosum with mental
retardation, ocular coloboma, and micrognathia (300472), Graham et al.
(2003) identified adjacent alterations in the 5-prime untranslated
region of the AUG translation initiation codon of the IGBP1 gene:
-57delT and -55T-A (300139.0001).
*FIELD* AV
.0001
CORPUS CALLOSUM, AGENESIS OF, WITH MENTAL RETARDATION, OCULAR COLOBOMA,
AND MICROGNATHIA
IGBP1, -57delT and -55T-A, 5-PRIME UTR
In 2 brothers with agenesis of the corpus callosum with mental
retardation, ocular coloboma, and micrognathia (300472), Graham et al.
(2003) identified adjacent alterations in the region just 5-prime of the
AUG translation initiation codon of the IGBP1 gene: -57delT and -55T-A.
Western blot analysis following normalization to HDAC1 (601241) revealed
an approximately 20% increase in IGBP1 levels over that seen in controls
in the fibroblasts of 1 of the brothers. The mother was shown to be a
carrier of both changes, which were located in the 5-prime UTR of the
gene. The altered sequence was not present in the mother's half brother
or in her maternal grandmother.
*FIELD* RF
1. Di Como, C. J.; Arndt, K. T.: Nutrients, via the Tor proteins,
stimulate the association of Tap42 with type 2A phosphatases. Genes
Dev. 10: 1904-1916, 1996.
2. Graham, J. M., Jr.; Wheeler, P.; Tackels-Horne, D.; Lin, A. E.;
Hall, B. D.; May, M.; Short, K. M.; Schwartz, C. E.; Cox, T. C.:
A new X-linked syndrome with agenesis of the corpus callosum, mental
retardation, coloboma, micrognathia, and a mutation in the alpha 4
gene at Xq13. Am. J. Med. Genet. 123A: 37-44, 2003.
3. Inui, S.; Kuwahara, K.; Mizutani, J.; Maeda, K.; Kawai, T.; Nakayasu,
H.; Sakaguchi, N.: Molecular cloning of a cDNA clone encoding a phosphoprotein
component related to the Ig receptor-mediated signal transduction. J.
Immun. 154: 2714-2723, 1995.
4. Kong, M.; Fox, C. J.; Mu, J.; Solt, L.; Xu, A.; Cinalli, R. M.;
Birnbaum, M. J.; Lindsten, T.; Thompson, C. B.: The PP2A-associated
protein alpha-4 is an essential inhibitor of apoptosis. Science 306:
695-698, 2004.
5. Liu, J.; Prickett, T. D.; Elliott, E.; Meroni, G.; Brautigan, D.
L.: Phosphorylation and microtubule association of the Opitz syndrome
protein mid-1 is regulated by protein phosphatase 2A via binding to
the regulatory subunit alpha-4. Proc. Nat. Acad. Sci. 98: 6650-6655,
2001.
6. Onda, M.; Inui, S.; Maeda, K.; Suzuki, M.; Takahashi, E.; Sakaguchi,
N.: Expression and chromosomal localization of the human alpha-4/IGBP1
gene, the structure of which is closely related to the yeast TAP42
protein of the rapamycin-sensitive signal transduction pathway. Genomics 46:
373-378, 1997.
*FIELD* CN
Matthew B. Gross - updated: 6/20/2008
Ada Hamosh - updated: 6/2/2005
*FIELD* CD
Sheryl A. Jankowski: 7/23/1998
*FIELD* ED
mgross: 11/02/2010
mgross: 6/20/2008
wwang: 3/10/2008
tkritzer: 6/3/2005
terry: 6/2/2005
tkritzer: 2/3/2004
carol: 7/24/1998
dholmes: 7/23/1998
*RECORD*
*FIELD* NO
300139
*FIELD* TI
*300139 IMMUNOGLOBULIN-BINDING PROTEIN 1; IGBP1
;;PROTEIN PHOSPHATASE 2A, REGULATORY SUBUNIT ALPHA-4;;
read moreALPHA-4
*FIELD* TX
CLONING
The proliferation and differentiation of B cells is dependent upon a
B-cell antigen receptor (BCR) complex. Binding of antigens to specific
B-cell receptors results in a tyrosine phosphorylation reaction through
the BCR complex and leads to multiple signal transduction pathways. The
murine Igbp1 gene encodes a protein that coprecipitates with the MB1
(112205) protein of the BCR complex and has a possible SH3-binding motif
and multiple sites that are phosphorylated by protein kinase C under
phorbol myristate acetate activation (Inui et al., 1995). TAP42, a yeast
gene similar to Igbp1, is associated with phosphatase 2A or Sit4, all of
which are critical for the survival of yeast cells in the
rapamycin-sensitive signal transduction pathways (Di Como and Arndt,
1996). Onda et al. (1997) demonstrated the existence of an
Igbp1/TAP42-related gene in humans by Southern blot analysis with the
mouse Igbp1 cDNA probe on a DNA zoo blot. They used the mouse probe to
isolate 2 overlapping cDNA clones from a human B-cell line. The IGBP1
cDNA encodes a potential polypeptide of 339 amino acids with 82.9% amino
acid sequence homology to mouse Igbp1. This putative protein contains 4
potential N-glycosylation sites, 2 myristylation sites, 6 possible
phosphorylation sites with protein kinase C and 7 with casein kinase II,
and an amino acid stretch related to the SH3-binding consensus sequence
in a similar position to that found in mouse Igbp1 and yeast TAP42. By
Northern blot analysis, Onda et al. (1997) detected ubiquitous
expression of IGBP1 as a 1.4-kb mRNA, with highest levels of expression
found in heart, skeletal muscle, and pancreas. Antibodies against an
IGBP1 fusion protein detected a single band of 45 kD in Western blots
from human lymphoid cell lines.
GENE FUNCTION
Wildtype Mid1 (300552) colocalizes predominantly with microtubules, in
contrast to mutant versions of Mid1 found in Opitz syndrome (300000)
patients that appear clustered in the cytosol. Using yeast 2-hybrid
screening, Liu et al. (2001) found that the alpha-4 subunit of protein
phosphatases-2A, -4, and -6 bound Mid1. Localization of Mid1 and the
alpha-4 subunit was influenced by one another in transiently transfected
cells. Mid1 could recruit the alpha-4 subunit onto microtubules, and
high levels of the alpha-4 subunit could displace Mid1 into the cytosol.
Metabolic (32)P labeling of cells revealed Mid1 to be a phosphoprotein,
and coexpression of the full-length alpha-4 subunit decreased Mid1
phosphorylation, indicative of a functional interaction. Association of
GFP-Mid1 with microtubules in living cells was perturbed by inhibitors
of MAP kinase activation. Liu et al. (2001) concluded that Mid1
association with microtubules, which seems important for normal midline
development, is regulated by dynamic phosphorylation involving MAP
kinase and protein phosphatase that is targeted specifically to Mid1 by
the alpha-4 subunit.
Kong et al. (2004) demonstrated that alpha-4 is required to repress
apoptosis in mouse cells. Alpha-4 is a nonredundant regulator of the
dephosphorylation of the transcription factors c-Jun and p53 (191170).
As a result of alpha-4 deletion, multiple proapoptotic genes were
transcribed. Either inhibition of new protein synthesis or Bcl-x(L)
expression suppressed apoptosis initiated by alpha-4 deletion. Kong et
al. (2004) concluded that mammalian cell viability depends on repression
of transcription-initiated apoptosis mediated by a component of PP2A.
MAPPING
By fluorescence in situ hybridization, Onda et al. (1997) isolated a
genomic human BAC clone of IGBP1 and mapped the gene to chromosome
Xq13.1-13.3.
MOLECULAR GENETICS
In 2 brothers with agenesis of the corpus callosum with mental
retardation, ocular coloboma, and micrognathia (300472), Graham et al.
(2003) identified adjacent alterations in the 5-prime untranslated
region of the AUG translation initiation codon of the IGBP1 gene:
-57delT and -55T-A (300139.0001).
*FIELD* AV
.0001
CORPUS CALLOSUM, AGENESIS OF, WITH MENTAL RETARDATION, OCULAR COLOBOMA,
AND MICROGNATHIA
IGBP1, -57delT and -55T-A, 5-PRIME UTR
In 2 brothers with agenesis of the corpus callosum with mental
retardation, ocular coloboma, and micrognathia (300472), Graham et al.
(2003) identified adjacent alterations in the region just 5-prime of the
AUG translation initiation codon of the IGBP1 gene: -57delT and -55T-A.
Western blot analysis following normalization to HDAC1 (601241) revealed
an approximately 20% increase in IGBP1 levels over that seen in controls
in the fibroblasts of 1 of the brothers. The mother was shown to be a
carrier of both changes, which were located in the 5-prime UTR of the
gene. The altered sequence was not present in the mother's half brother
or in her maternal grandmother.
*FIELD* RF
1. Di Como, C. J.; Arndt, K. T.: Nutrients, via the Tor proteins,
stimulate the association of Tap42 with type 2A phosphatases. Genes
Dev. 10: 1904-1916, 1996.
2. Graham, J. M., Jr.; Wheeler, P.; Tackels-Horne, D.; Lin, A. E.;
Hall, B. D.; May, M.; Short, K. M.; Schwartz, C. E.; Cox, T. C.:
A new X-linked syndrome with agenesis of the corpus callosum, mental
retardation, coloboma, micrognathia, and a mutation in the alpha 4
gene at Xq13. Am. J. Med. Genet. 123A: 37-44, 2003.
3. Inui, S.; Kuwahara, K.; Mizutani, J.; Maeda, K.; Kawai, T.; Nakayasu,
H.; Sakaguchi, N.: Molecular cloning of a cDNA clone encoding a phosphoprotein
component related to the Ig receptor-mediated signal transduction. J.
Immun. 154: 2714-2723, 1995.
4. Kong, M.; Fox, C. J.; Mu, J.; Solt, L.; Xu, A.; Cinalli, R. M.;
Birnbaum, M. J.; Lindsten, T.; Thompson, C. B.: The PP2A-associated
protein alpha-4 is an essential inhibitor of apoptosis. Science 306:
695-698, 2004.
5. Liu, J.; Prickett, T. D.; Elliott, E.; Meroni, G.; Brautigan, D.
L.: Phosphorylation and microtubule association of the Opitz syndrome
protein mid-1 is regulated by protein phosphatase 2A via binding to
the regulatory subunit alpha-4. Proc. Nat. Acad. Sci. 98: 6650-6655,
2001.
6. Onda, M.; Inui, S.; Maeda, K.; Suzuki, M.; Takahashi, E.; Sakaguchi,
N.: Expression and chromosomal localization of the human alpha-4/IGBP1
gene, the structure of which is closely related to the yeast TAP42
protein of the rapamycin-sensitive signal transduction pathway. Genomics 46:
373-378, 1997.
*FIELD* CN
Matthew B. Gross - updated: 6/20/2008
Ada Hamosh - updated: 6/2/2005
*FIELD* CD
Sheryl A. Jankowski: 7/23/1998
*FIELD* ED
mgross: 11/02/2010
mgross: 6/20/2008
wwang: 3/10/2008
tkritzer: 6/3/2005
terry: 6/2/2005
tkritzer: 2/3/2004
carol: 7/24/1998
dholmes: 7/23/1998
MIM
300472
*RECORD*
*FIELD* NO
300472
*FIELD* TI
#300472 CORPUS CALLOSUM, AGENESIS OF, WITH MENTAL RETARDATION, OCULAR COLOBOMA,
AND MICROGNATHIA
read more;;MENTAL RETARDATION, X-LINKED, SYNDROMIC 28; MRXS28
*FIELD* TX
A number sign (#) is used with this entry because agenesis of the corpus
callosum with mental retardation, ocular coloboma, and micrognathia is
caused by mutation in the IGBP1 gene (300139).
CLINICAL FEATURES
Graham et al. (2003) described 2 brothers with a seemingly unique
pattern of malformations that included coloboma of the iris and optic
nerve, high forehead, severe retrognathia, mental retardation, and
agenesis of the corpus callosum. Both boys had low-set cupped ears with
sensorineural hearing loss, pectus excavatum, scoliosis, and short
stature. One brother had choanal atresia and cardiac defects in the form
of ventricular septal defect (VSD) and patent ductus arteriosus (PDA)
which resolved spontaneously.
MOLECULAR GENETICS
Because agenesis of the corpus callosum and the distinctive facial
features were reminiscent of FG syndrome (305450), Graham et al. (2003)
analyzed DNA for markers linked to the FGS1 locus at Xq13-q21. The
brothers were concordant for markers spanning this presumed FG region,
and in both Graham et al. (2003) identified adjacent alterations in the
region just 5-prime of the AUG translation initiation codon of the IGBP1
gene (which they called alpha-4): -57delT and 55T-A (300139.0001). The
mother was shown to be a carrier of both changes, which were located in
the 5-prime UTR of the gene. The altered sequence was not present in the
mother's half brother or in her maternal grandmother. It also was not
found in the DNA from 410 control chromosomes or in the DNA from
patients with mental retardation syndromes that map to this region, and
was not found in patients with Opitz G/BBB syndrome (300000) in whom no
mutation in MID1 (300552) had been detected. The last testing was done
because of the demonstrated interaction between alpha-4 and MID1.
*FIELD* RF
1. Graham, J. M., Jr.; Wheeler, P.; Tackels-Horne, D.; Lin, A. E.;
Hall, B. D.; May, M.; Short, K. M.; Schwartz, C. E.; Cox, T. C.:
A new X-linked syndrome with agenesis of the corpus callosum, mental
retardation, coloboma, micrognathia, and a mutation in the alpha 4
gene at Xq13. Am. J. Med. Genet. 123A: 37-44, 2003.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Head];
Macrocephaly;
[Face];
High forehead;
Retrognathia;
[Ears];
Low-set ears;
Cupped ears;
Sensorineural hearing loss;
[Eyes];
Coloboma (iris or optic nerve);
Impaired vision;
Downslanting palpebral fissures;
[Mouth];
High-arched palate;
[Neck];
Short neck;
Broad neck
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Pectus excavatum
SKELETAL:
[Spine];
Scoliosis
NEUROLOGIC:
[Central nervous system];
Agenesis of the corpus callosum;
Mental retardation
MOLECULAR BASIS:
Caused by mutation in the immunoglobulin-binding protein-1 gene (IGBP1,
300139.0001)
*FIELD* CD
Cassandra L. Kniffin: 2/24/2004
*FIELD* ED
joanna: 03/15/2004
ckniffin: 2/24/2004
*FIELD* CD
Victor A. McKusick: 1/15/2004
*FIELD* ED
carol: 10/26/2011
ckniffin: 10/25/2011
carol: 8/9/2005
tkritzer: 2/3/2004
tkritzer: 1/16/2004
*RECORD*
*FIELD* NO
300472
*FIELD* TI
#300472 CORPUS CALLOSUM, AGENESIS OF, WITH MENTAL RETARDATION, OCULAR COLOBOMA,
AND MICROGNATHIA
read more;;MENTAL RETARDATION, X-LINKED, SYNDROMIC 28; MRXS28
*FIELD* TX
A number sign (#) is used with this entry because agenesis of the corpus
callosum with mental retardation, ocular coloboma, and micrognathia is
caused by mutation in the IGBP1 gene (300139).
CLINICAL FEATURES
Graham et al. (2003) described 2 brothers with a seemingly unique
pattern of malformations that included coloboma of the iris and optic
nerve, high forehead, severe retrognathia, mental retardation, and
agenesis of the corpus callosum. Both boys had low-set cupped ears with
sensorineural hearing loss, pectus excavatum, scoliosis, and short
stature. One brother had choanal atresia and cardiac defects in the form
of ventricular septal defect (VSD) and patent ductus arteriosus (PDA)
which resolved spontaneously.
MOLECULAR GENETICS
Because agenesis of the corpus callosum and the distinctive facial
features were reminiscent of FG syndrome (305450), Graham et al. (2003)
analyzed DNA for markers linked to the FGS1 locus at Xq13-q21. The
brothers were concordant for markers spanning this presumed FG region,
and in both Graham et al. (2003) identified adjacent alterations in the
region just 5-prime of the AUG translation initiation codon of the IGBP1
gene (which they called alpha-4): -57delT and 55T-A (300139.0001). The
mother was shown to be a carrier of both changes, which were located in
the 5-prime UTR of the gene. The altered sequence was not present in the
mother's half brother or in her maternal grandmother. It also was not
found in the DNA from 410 control chromosomes or in the DNA from
patients with mental retardation syndromes that map to this region, and
was not found in patients with Opitz G/BBB syndrome (300000) in whom no
mutation in MID1 (300552) had been detected. The last testing was done
because of the demonstrated interaction between alpha-4 and MID1.
*FIELD* RF
1. Graham, J. M., Jr.; Wheeler, P.; Tackels-Horne, D.; Lin, A. E.;
Hall, B. D.; May, M.; Short, K. M.; Schwartz, C. E.; Cox, T. C.:
A new X-linked syndrome with agenesis of the corpus callosum, mental
retardation, coloboma, micrognathia, and a mutation in the alpha 4
gene at Xq13. Am. J. Med. Genet. 123A: 37-44, 2003.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Head];
Macrocephaly;
[Face];
High forehead;
Retrognathia;
[Ears];
Low-set ears;
Cupped ears;
Sensorineural hearing loss;
[Eyes];
Coloboma (iris or optic nerve);
Impaired vision;
Downslanting palpebral fissures;
[Mouth];
High-arched palate;
[Neck];
Short neck;
Broad neck
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Pectus excavatum
SKELETAL:
[Spine];
Scoliosis
NEUROLOGIC:
[Central nervous system];
Agenesis of the corpus callosum;
Mental retardation
MOLECULAR BASIS:
Caused by mutation in the immunoglobulin-binding protein-1 gene (IGBP1,
300139.0001)
*FIELD* CD
Cassandra L. Kniffin: 2/24/2004
*FIELD* ED
joanna: 03/15/2004
ckniffin: 2/24/2004
*FIELD* CD
Victor A. McKusick: 1/15/2004
*FIELD* ED
carol: 10/26/2011
ckniffin: 10/25/2011
carol: 8/9/2005
tkritzer: 2/3/2004
tkritzer: 1/16/2004