Full text data of SORBS1
SORBS1
(KIAA0894, KIAA1296, SH3D5)
[Confidence: low (only semi-automatic identification from reviews)]
Sorbin and SH3 domain-containing protein 1 (Ponsin; SH3 domain protein 5; SH3P12; c-Cbl-associated protein; CAP)
Sorbin and SH3 domain-containing protein 1 (Ponsin; SH3 domain protein 5; SH3P12; c-Cbl-associated protein; CAP)
UniProt
Q9BX66
ID SRBS1_HUMAN Reviewed; 1292 AA.
AC Q9BX66; A0AED4; A6NEK3; A6NID8; A6NJS4; A7MD40; D3DR42; O43857;
read moreAC Q5T923; Q5T924; Q5T927; Q5T928; Q5T929; Q5T930; Q5T931; Q5T932;
AC Q7LBE5; Q8IVK0; Q8IVQ4; Q96KF3; Q96KF4; Q9BX64; Q9BX65; Q9P2Q0;
AC Q9UFT2; Q9UHN7; Q9Y338;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Sorbin and SH3 domain-containing protein 1;
DE AltName: Full=Ponsin;
DE AltName: Full=SH3 domain protein 5;
DE AltName: Full=SH3P12;
DE AltName: Full=c-Cbl-associated protein;
DE Short=CAP;
GN Name=SORBS1; Synonyms=KIAA0894, KIAA1296, SH3D5;
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] (ISOFORMS 1; 2; 3 AND 4), TISSUE
RP SPECIFICITY, INTERACTION WITH ABL1 AND INSULIN RECEPTOR, AND VARIANT
RP PRO-61.
RC TISSUE=Liver, and Skeletal muscle;
RX PubMed=11374898; DOI=10.1006/geno.2001.6541;
RA Lin W.-H., Huang C.-J., Liu M.-W., Chang H.-M., Chen Y.-J., Tai T.-Y.,
RA Chuang L.-M.;
RT "Cloning, mapping, and characterization of the human sorbin and SH3
RT domain containing 1 (SORBS1) gene: a protein associated with c-Abl
RT during insulin signaling in the hepatoma cell line Hep3B.";
RL Genomics 74:12-20(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), SUBCELLULAR LOCATION,
RP INTERACTION WITH SCA7, AND VARIANT PRO-61.
RC TISSUE=Retina;
RX PubMed=11371513; DOI=10.1093/hmg/10.11.1201;
RA Lebre A.-S., Jamot L., Takahashi J., Spassky N., Leprince C.,
RA Ravise N., Zander C., Fujigasaki H., Kussel-Andermann P.,
RA Duyckaerts C., Camonis J.H., Brice A.;
RT "Ataxin-7 interacts with a Cbl-associated protein that it recruits
RT into neuronal intranuclear inclusions.";
RL Hum. Mol. Genet. 10:1201-1213(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND VARIANTS PRO-61; TRP-74
RP AND ALA-237.
RC TISSUE=Skeletal muscle;
RX PubMed=11532984; DOI=10.1093/hmg/10.17.1753;
RA Lin W.-H., Chiu K.C., Chang H.-M., Lee K.C., Tai T.-Y., Chuang L.-M.;
RT "Molecular scanning of the human sorbin and SH3-domain-containing-1
RT (SORBS1) gene: positive association of the T228A polymorphism with
RT obesity and type 2 diabetes.";
RL Hum. Mol. Genet. 10:1753-1760(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), INTERACTION WITH INPPL1, AND
RP VARIANT PRO-61.
RC TISSUE=Brain;
RX PubMed=12504111; DOI=10.1016/S0006-291X(02)02894-2;
RA Vandenbroere I., Paternotte N., Dumont J.E., Erneux C., Pirson I.;
RT "The c-Cbl-associated protein and c-Cbl are two new partners of the
RT SH2-containing inositol polyphosphate 5-phosphatase SHIP2.";
RL Biochem. Biophys. Res. Commun. 300:494-500(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11), INTERACTION WITH PXN, X-RAY
RP CRYSTALLOGRAPHY (0.83 ANGSTROMS) OF 870-930 IN COMPLEX WITH PXN
RP PEPTIDE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT PRO-61.
RC TISSUE=Skeletal muscle;
RX PubMed=17462669; DOI=10.1016/j.jmb.2007.03.050;
RA Gehmlich K., Pinotsis N., Hayess K., van der Ven P.F., Milting H.,
RA El Banayosy A., Korfer R., Wilmanns M., Ehler E., Furst D.O.;
RT "Paxillin and ponsin interact in nascent costameres of muscle cells.";
RL J. Mol. Biol. 369:665-682(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9), AND VARIANT
RP PRO-61.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10), AND VARIANT
RP PRO-61.
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 9), AND VARIANT
RP PRO-61.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 752-888.
RC TISSUE=Placenta;
RA Hachiya T., Kobayasi A., Touji S., Tamai K.;
RT "A Fas-ligand associated factor 2, FLAF2, potentiates Fas-ligand
RT stability.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86; SER-89; SER-472;
RP SER-665; THR-862 AND SER-945, PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-478 AND SER-735 (ISOFORM 10), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-1213 (ISOFORM 12), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-346 AND SER-603 (ISOFORM 4), PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-923 (ISOFORM 5), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-765 (ISOFORM 6), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-469 (ISOFORM 7), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-730 (ISOFORM 8), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-387 AND SER-700 (ISOFORM 9), AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 870-930.
RX PubMed=17784760; DOI=10.1021/ja073846c;
RA Margiolaki I., Wright J.P., Wilmanns M., Fitch A.N., Pinotsis N.;
RT "Second SH3 domain of ponsin solved from powder diffraction.";
RL J. Am. Chem. Soc. 129:11865-11871(2007).
RN [17]
RP STRUCTURE BY NMR OF 796-926.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of SH3 domains of human Sorbin and SH3 domain-
RT containing protein 1.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [18]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-195.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Plays a role in tyrosine phosphorylation of CBL by
CC linking CBL to the insulin receptor. Required for insulin-
CC stimulated glucose transport. Involved in formation of actin
CC stress fibers and focal adhesions (By similarity).
CC -!- SUBUNIT: Interacts (via third SH3 domain) with the Ten-1 ICD form
CC of TENM1; the interaction induces the translocation of SORBS1 to
CC the nucleus (By similarity). Interacts with the long isoform of
CC MLLT4/afadin and with VCL. MLLT4 and VCL bind to SORBS1 in a
CC competitive manner and do not form a ternary complex. Interacts
CC with ABL1, CBL, CBLB and INPPL1/SHIP2 through the third SH3
CC domain. Interaction with ABL1 occurs only after insulin
CC stimulation while this has no effect on the interaction with
CC INPPL1. Interacts with the insulin receptor but dissociates from
CC it following insulin stimulation. Also interacts with SCA7,
CC PTK2/FAK1 and flotillin. Interacts (via SH3 domain 2) with PXN.
CC -!- INTERACTION:
CC P00519:ABL1; NbExp=2; IntAct=EBI-433642, EBI-375543;
CC O15265:ATXN7; NbExp=15; IntAct=EBI-433642, EBI-708350;
CC P39052:Dnm2 (xeno); NbExp=5; IntAct=EBI-433642, EBI-349613;
CC O15357:INPPL1; NbExp=5; IntAct=EBI-433642, EBI-1384248;
CC Q13177:PAK2; NbExp=2; IntAct=EBI-433642, EBI-1045887;
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction. Cell
CC membrane. Cytoplasm, cytoskeleton. Cell junction, focal adhesion.
CC Nucleus (By similarity). Nucleus matrix (By similarity).
CC Note=Colocalizes with the Ten-1 ICD form of TENM1 in the nucleus
CC (By similarity). Colocalizes with actin stress fibers. Also
CC detected at the plasma membrane and in neuronal intranuclear
CC inclusions. Colocalized with PXN at focal adhesions during
CC myogenic differentiation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=12;
CC Name=1;
CC IsoId=Q9BX66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BX66-2; Sequence=VSP_050902, VSP_050910;
CC Note=Ref.1 (AAK37564) sequence is in conflict in positions:
CC 435:K->E, 452-455:AHCS->SRCG, 463:N->D;
CC Name=3;
CC IsoId=Q9BX66-3; Sequence=VSP_050898, VSP_050900, VSP_050906,
CC VSP_050912, VSP_050913;
CC Name=4;
CC IsoId=Q9BX66-4; Sequence=VSP_050895, VSP_050896, VSP_050899,
CC VSP_050900, VSP_050903, VSP_050907,
CC VSP_050911;
CC Note=Contains a phosphoserine at position 346. Contains a
CC phosphoserine at position 603;
CC Name=5;
CC IsoId=Q9BX66-5; Sequence=VSP_050896, VSP_050901, VSP_050911;
CC Note=Contains a phosphoserine at position 923;
CC Name=6;
CC IsoId=Q9BX66-6; Sequence=VSP_050896, VSP_050899, VSP_050905,
CC VSP_050911;
CC Note=Contains a phosphoserine at position 765;
CC Name=7;
CC IsoId=Q9BX66-7; Sequence=VSP_050895, VSP_050896, VSP_050900,
CC VSP_050903, VSP_050908, VSP_050909;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 469;
CC Name=8;
CC IsoId=Q9BX66-8; Sequence=VSP_050895, VSP_050899, VSP_050900,
CC VSP_050904, VSP_050911;
CC Note=Contains a phosphoserine at position 730;
CC Name=9;
CC IsoId=Q9BX66-9; Sequence=VSP_050899, VSP_050900, VSP_050903,
CC VSP_050911;
CC Note=Contains a phosphoserine at position 387. Contains a
CC phosphoserine at position 700;
CC Name=10;
CC IsoId=Q9BX66-10; Sequence=VSP_050895, VSP_050900, VSP_050903,
CC VSP_050907, VSP_050911;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 478. Contains a phosphoserine at
CC position 735;
CC Name=11;
CC IsoId=Q9BX66-11; Sequence=VSP_050900, VSP_039210;
CC Name=12;
CC IsoId=Q9BX66-12; Sequence=VSP_050895, VSP_050899, VSP_041193,
CC VSP_050900, VSP_050904, VSP_041194,
CC VSP_050911;
CC Note=No experimental confirmation available. Derived from mouse
CC ortholog data. Contains a phosphoserine at position 1213;
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle (at protein
CC level). Widely expressed with highest levels in heart and skeletal
CC muscle.
CC -!- PTM: O-glycosylated (By similarity).
CC -!- SIMILARITY: Contains 3 SH3 domains.
CC -!- SIMILARITY: Contains 1 SoHo domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB93496.1; Type=Frameshift; Positions=861, 867, 885;
CC Sequence=BAA92534.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AF136380; AAD27647.1; -; mRNA.
DR EMBL; AF356525; AAK37563.1; -; mRNA.
DR EMBL; AF356526; AAK37564.1; -; mRNA.
DR EMBL; AF356527; AAK37565.1; -; mRNA.
DR EMBL; AF330623; AAK57479.1; -; mRNA.
DR EMBL; AF330624; AAK57480.1; -; mRNA.
DR EMBL; AF136381; AAF22175.1; -; mRNA.
DR EMBL; AJ489942; CAD34588.1; -; mRNA.
DR EMBL; AM260536; CAJ97431.1; -; mRNA.
DR EMBL; AB037717; BAA92534.1; ALT_INIT; mRNA.
DR EMBL; AL117472; CAB55947.1; -; mRNA.
DR EMBL; AL158165; CAI14378.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14379.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14380.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14381.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14382.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14383.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14384.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14385.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49999.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW50007.1; -; Genomic_DNA.
DR EMBL; BC042612; AAH42612.1; -; mRNA.
DR EMBL; BC152463; AAI52464.1; -; mRNA.
DR EMBL; U70668; AAB93496.1; ALT_FRAME; mRNA.
DR PIR; T17257; T17257.
DR RefSeq; NP_001030126.1; NM_001034954.1.
DR RefSeq; NP_001030127.1; NM_001034955.1.
DR RefSeq; NP_001030128.1; NM_001034956.1.
DR RefSeq; NP_001030129.1; NM_001034957.1.
DR RefSeq; NP_006425.2; NM_006434.2.
DR RefSeq; NP_056200.1; NM_015385.2.
DR RefSeq; NP_079267.1; NM_024991.1.
DR RefSeq; XP_005269484.1; XM_005269427.1.
DR RefSeq; XP_005269490.1; XM_005269433.1.
DR RefSeq; XP_005269493.1; XM_005269436.1.
DR RefSeq; XP_005269495.1; XM_005269438.1.
DR UniGene; Hs.38621; -.
DR PDB; 2DL3; NMR; -; A=791-850.
DR PDB; 2ECZ; NMR; -; A=870-926.
DR PDB; 2LJ0; NMR; -; A=1228-1292.
DR PDB; 2LJ1; NMR; -; A=1228-1291.
DR PDB; 2O2W; X-ray; 2.27 A; A=870-930.
DR PDB; 2O31; X-ray; 1.50 A; A=870-930.
DR PDB; 2O9S; X-ray; 0.83 A; A=870-930.
DR PDB; 2O9V; X-ray; 1.63 A; A=870-930.
DR PDBsum; 2DL3; -.
DR PDBsum; 2ECZ; -.
DR PDBsum; 2LJ0; -.
DR PDBsum; 2LJ1; -.
DR PDBsum; 2O2W; -.
DR PDBsum; 2O31; -.
DR PDBsum; 2O9S; -.
DR PDBsum; 2O9V; -.
DR ProteinModelPortal; Q9BX66; -.
DR SMR; Q9BX66; 791-930, 1228-1292.
DR IntAct; Q9BX66; 24.
DR MINT; MINT-2792261; -.
DR PhosphoSite; Q9BX66; -.
DR DMDM; 215273913; -.
DR PaxDb; Q9BX66; -.
DR PRIDE; Q9BX66; -.
DR DNASU; 10580; -.
DR Ensembl; ENST00000277982; ENSP00000277982; ENSG00000095637.
DR Ensembl; ENST00000306402; ENSP00000302556; ENSG00000095637.
DR Ensembl; ENST00000347291; ENSP00000277985; ENSG00000095637.
DR Ensembl; ENST00000353505; ENSP00000343998; ENSG00000095637.
DR Ensembl; ENST00000354106; ENSP00000277984; ENSG00000095637.
DR Ensembl; ENST00000361941; ENSP00000355136; ENSG00000095637.
DR Ensembl; ENST00000371227; ENSP00000360271; ENSG00000095637.
DR Ensembl; ENST00000371239; ENSP00000360283; ENSG00000095637.
DR Ensembl; ENST00000371241; ENSP00000360285; ENSG00000095637.
DR Ensembl; ENST00000371245; ENSP00000360291; ENSG00000095637.
DR Ensembl; ENST00000371246; ENSP00000360292; ENSG00000095637.
DR Ensembl; ENST00000371247; ENSP00000360293; ENSG00000095637.
DR Ensembl; ENST00000371249; ENSP00000360295; ENSG00000095637.
DR Ensembl; ENST00000393949; ENSP00000377521; ENSG00000095637.
DR Ensembl; ENST00000607232; ENSP00000475901; ENSG00000095637.
DR GeneID; 10580; -.
DR KEGG; hsa:10580; -.
DR UCSC; uc001kkp.3; human.
DR CTD; 10580; -.
DR GeneCards; GC10M097061; -.
DR HGNC; HGNC:14565; SORBS1.
DR HPA; HPA027559; -.
DR HPA; HPA036994; -.
DR MIM; 605264; gene.
DR neXtProt; NX_Q9BX66; -.
DR PharmGKB; PA37899; -.
DR eggNOG; NOG256936; -.
DR HOVERGEN; HBG053053; -.
DR InParanoid; Q9BX66; -.
DR KO; K06086; -.
DR OMA; ITSEWIS; -.
DR OrthoDB; EOG75XGKP; -.
DR PhylomeDB; Q9BX66; -.
DR Reactome; REACT_17044; Muscle contraction.
DR SignaLink; Q9BX66; -.
DR ChiTaRS; SORBS1; human.
DR EvolutionaryTrace; Q9BX66; -.
DR GeneWiki; SORBS1; -.
DR GenomeRNAi; 10580; -.
DR NextBio; 40165; -.
DR PRO; PR:Q9BX66; -.
DR ArrayExpress; Q9BX66; -.
DR Bgee; Q9BX66; -.
DR Genevestigator; Q9BX66; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; ISS:BHF-UCL.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001725; C:stress fiber; ISS:UniProtKB.
DR GO; GO:0005915; C:zonula adherens; TAS:ProtInc.
DR GO; GO:0003779; F:actin binding; TAS:ProtInc.
DR GO; GO:0005158; F:insulin receptor binding; IDA:UniProtKB.
DR GO; GO:0005070; F:SH3/SH2 adaptor activity; ISS:BHF-UCL.
DR GO; GO:0048041; P:focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0015758; P:glucose transport; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:BHF-UCL.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0043149; P:stress fiber assembly; ISS:UniProtKB.
DR InterPro; IPR028506; CAP/ponsin.
DR InterPro; IPR011511; SH3_2.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR003127; Sorb.
DR PANTHER; PTHR10661:SF4; PTHR10661:SF4; 1.
DR Pfam; PF07653; SH3_2; 1.
DR Pfam; PF02208; Sorb; 1.
DR SMART; SM00326; SH3; 3.
DR SMART; SM00459; Sorb; 1.
DR SUPFAM; SSF50044; SSF50044; 3.
DR PROSITE; PS50002; SH3; 3.
DR PROSITE; PS50831; SOHO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Complete proteome; Cytoplasm; Cytoskeleton; Glycoprotein; Membrane;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW SH3 domain; Transport.
FT CHAIN 1 1292 Sorbin and SH3 domain-containing protein
FT 1.
FT /FTId=PRO_0000072185.
FT DOMAIN 366 469 SoHo.
FT DOMAIN 793 852 SH3 1.
FT DOMAIN 867 928 SH3 2.
FT DOMAIN 1231 1292 SH3 3.
FT MOD_RES 86 86 Phosphoserine.
FT MOD_RES 89 89 Phosphoserine.
FT MOD_RES 369 369 Phosphoserine (By similarity).
FT MOD_RES 472 472 Phosphoserine.
FT MOD_RES 481 481 Phosphoserine.
FT MOD_RES 536 536 Phosphotyrosine; by ABL1 (By similarity).
FT MOD_RES 654 654 Phosphotyrosine; by ABL1 (By similarity).
FT MOD_RES 665 665 Phosphoserine.
FT MOD_RES 862 862 Phosphothreonine.
FT MOD_RES 945 945 Phosphoserine.
FT MOD_RES 1240 1240 Phosphotyrosine; by ABL1 (By similarity).
FT VAR_SEQ 26 57 Missing (in isoform 4, isoform 7, isoform
FT 8, isoform 10 and isoform 12).
FT /FTId=VSP_050895.
FT VAR_SEQ 101 109 Missing (in isoform 4, isoform 5, isoform
FT 6 and isoform 7).
FT /FTId=VSP_050896.
FT VAR_SEQ 147 215 Missing (in isoform 3).
FT /FTId=VSP_050898.
FT VAR_SEQ 148 270 Missing (in isoform 4, isoform 6, isoform
FT 8, isoform 9 and isoform 12).
FT /FTId=VSP_050899.
FT VAR_SEQ 319 328 Missing (in isoform 12).
FT /FTId=VSP_041193.
FT VAR_SEQ 408 453 Missing (in isoform 3, isoform 4, isoform
FT 7, isoform 8, isoform 9, isoform 10,
FT isoform 11 and isoform 12).
FT /FTId=VSP_050900.
FT VAR_SEQ 431 451 Missing (in isoform 5).
FT /FTId=VSP_050901.
FT VAR_SEQ 434 453 DNPYTPTYQFPASTPSPKSE -> TKSCSVMSPRLECSGTV
FT IAHCSLKLLDSSNPPTSASQVAGTA (in isoform 2).
FT /FTId=VSP_050902.
FT VAR_SEQ 552 635 Missing (in isoform 4, isoform 7, isoform
FT 9 and isoform 10).
FT /FTId=VSP_050903.
FT VAR_SEQ 580 635 Missing (in isoform 6).
FT /FTId=VSP_050905.
FT VAR_SEQ 580 601 Missing (in isoform 8 and isoform 12).
FT /FTId=VSP_050904.
FT VAR_SEQ 602 635 Missing (in isoform 3).
FT /FTId=VSP_050906.
FT VAR_SEQ 709 709 K -> KVDRKGGNAHMISSSSVHSRTFNTSNALGPVCKHKK
FT PLSAAKACISEILPSKFKPRLSAPSALLQEQKSILLPSEKA
FT QSCENLCVSGSLNDSKRGLPLQVGGSIENLLMRSRRDYDSK
FT SSSTMSLQEYSTSGRRPCPLSRKAGMQFTMLYRDMHQINRS
FT GLFLGSISSSSSVRDLASHFEKSSLALSRGELGPSQEGSEH
FT IPKHTVSSRITAFEQLIQRSRSMPSLDLSGRLSKSPTPVLS
FT RGSLTSARSAESLLESTKLHPKEMDGMNSSGVYASPTCSNM
FT AHHALSFRGLVPSEPLSTCSDDVDRCSNISTDSREGSGGSV
FT HGDFPKHRLNKCKGTCPASYTRFTTIRKHEQQQTSRQPEWR
FT LDARGDKSTLLRNIYLMSPLPFRLKKPLHHHPRQPSPGDSS
FT GLLVGQKPDLPSQPHQDQPPSGGKPVVPTRLSSRHTMARLS
FT RSSEPSQERPTALEDYPRAINNGNSVPYSDHSLDRNNNPQS
FT ELAPSRG (in isoform 12).
FT /FTId=VSP_041194.
FT VAR_SEQ 738 793 Missing (in isoform 4 and isoform 10).
FT /FTId=VSP_050907.
FT VAR_SEQ 795 799 MRPAR -> KYDWA (in isoform 7).
FT /FTId=VSP_050908.
FT VAR_SEQ 800 1292 Missing (in isoform 7).
FT /FTId=VSP_050909.
FT VAR_SEQ 955 1212 Missing (in isoform 4, isoform 5, isoform
FT 6, isoform 8, isoform 9, isoform 10 and
FT isoform 12).
FT /FTId=VSP_050911.
FT VAR_SEQ 955 1117 Missing (in isoform 2).
FT /FTId=VSP_050910.
FT VAR_SEQ 956 975 FSSHSKLITPAPSSLPHSRR -> LSHHSLRAGPDLTESEK
FT SYV (in isoform 3).
FT /FTId=VSP_050912.
FT VAR_SEQ 976 1213 Missing (in isoform 3).
FT /FTId=VSP_050913.
FT VAR_SEQ 1213 1213 Q -> QLSHHSLRAGPDLTESEKSYV (in isoform
FT 11).
FT /FTId=VSP_039210.
FT VARIANT 61 61 L -> P (in dbSNP:rs943542).
FT /FTId=VAR_047652.
FT VARIANT 74 74 R -> W.
FT /FTId=VAR_019653.
FT VARIANT 175 175 G -> V (in dbSNP:rs7081076).
FT /FTId=VAR_047653.
FT VARIANT 195 195 T -> A (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035661.
FT VARIANT 237 237 T -> A (has a protective role in both
FT obesity and diabetes; dbSNP:rs2281939).
FT /FTId=VAR_019654.
FT VARIANT 485 485 Y -> C (in dbSNP:rs35808802).
FT /FTId=VAR_047654.
FT CONFLICT 9 9 S -> P (in Ref. 5; CAJ97431).
FT CONFLICT 18 18 P -> S (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 110 110 D -> G (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 113 113 R -> K (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 131 131 A -> V (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 134 134 Y -> S (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 226 228 RAS -> SAC (in Ref. 3; AAF22175).
FT CONFLICT 264 264 T -> P (in Ref. 3; AAF22175).
FT CONFLICT 292 295 PSVS -> SSEC (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 481 481 S -> R (in Ref. 3; AAF22175).
FT CONFLICT 489 489 E -> V (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 607 607 D -> E (in Ref. 3; AAF22175).
FT CONFLICT 610 610 L -> F (in Ref. 3; AAF22175).
FT CONFLICT 644 644 E -> G (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 679 679 R -> S (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 690 690 D -> V (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 694 694 Q -> R (in Ref. 5; CAJ97431).
FT CONFLICT 695 695 G -> D (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 710 710 D -> N (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 1156 1156 V -> G (in Ref. 1; AAK37563/AAK37564).
FT STRAND 796 802
FT STRAND 819 824
FT STRAND 830 834
FT STRAND 839 843
FT TURN 844 846
FT STRAND 847 849
FT STRAND 870 874
FT STRAND 893 899
FT STRAND 901 908
FT TURN 910 912
FT STRAND 915 919
FT HELIX 920 922
FT STRAND 923 927
FT STRAND 1230 1233
FT STRAND 1235 1240
FT STRAND 1257 1263
FT STRAND 1267 1273
FT TURN 1274 1276
FT STRAND 1279 1283
FT STRAND 1286 1289
SQ SEQUENCE 1292 AA; 142513 MW; 70DA4169B6D82F06 CRC64;
MSSECDGGSK AVMNGLAPGS NGQDKATADP LRARSISAVK IIPVKTVKNA SGLVLPTDMD
LTKICTGKGA VTLRASSSYR ETPSSSPASP QETRQHESKP GLEPEPSSAD EWRLSSSADA
NGNAQPSSLA AKGYRSVHPN LPSDKSQDAT SSSAAQPEVI VVPLYLVNTD RGQEGTARPP
TPLGPLGCVP TIPATASAAS PLTFPTLDDF IPPHLQRWPH HSQPARASGS FAPISQTPPS
FSPPPPLVPP APEDLRRVSE PDLTGAVSST DSSPLLNEVS SSLIGTDSQA FPSVSKPSSA
YPSTTIVNPT IVLLQHNREQ QKRLSSLSDP VSERRVGEQD SAPTQEKPTS PGKAIEKRAK
DDSRRVVKST QDLSDVSMDE VGIPLRNTER SKDWYKTMFK QIHKLNRDTP EENPYFPTYK
FPELPEIQQT SEEDNPYTPT YQFPASTPSP KSEDDDSDLY SPRYSFSEDT KSPLSVPRSK
SEMSYIDGEK VVKRSATLPL PARSSSLKSS SERNDWEPPD KKVDTRKYRA EPKSIYEYQP
GKSSVLTNEK MSRDISPEEI DLKNEPWYKF FSELEFGKPP PKKIWDYTPG DCSILPREDR
KTNLDKDLSL CQTELEADLE KMETLNKAPS ANVPQSSAIS PTPEISSETP GYIYSSNFHA
VKRESDGAPG DLTSLENERQ IYKSVLEGGD IPLQGLSGLK RPSSSASTKD SESPRHFIPA
DYLESTEEFI RRRHDDKEKL LADQRRLKRE QEEADIAARR HTGVIPTHHQ FITNERFGDL
LNIDDTAKRK SGSEMRPARA KFDFKAQTLK ELPLQKGDIV YIYKQIDQNW YEGEHHGRVG
IFPRTYIELL PPAEKAQPKK LTPVQVLEYG EAIAKFNFNG DTQVEMSFRK GERITLLRQV
DENWYEGRIP GTSRQGIFPI TYVDVIKRPL VKNPVDYMDL PFSSSPSRSA TASPQFSSHS
KLITPAPSSL PHSRRALSPE MHAVTSEWIS LTVGVPGRRS LALTPPLPPL PEASIYNTDH
LALSPRASPS LSLSLPHLSW SDRPTPRSVA SPLALPSPHK TYSLAPTSQA SLHMNGDGGV
HTPSSGIHQD SFLQLPLGSS DSVISQLSDA FSSQSKRQPW REESGQYERK AERGAGERGP
GGPKISKKSC LKPSDVVRCL STEQRLSDLN TPEESRPGKP LGSAFPGSEA EQTERHRGGE
QAGRKAARRG GSQQPQAQQR RVTPDRSQTS QDLFSYQALY SYIPQNDDEL ELRDGDIVDV
MEKCDDGWFV GTSRRTKQFG TFPGNYVKPL YL
//
ID SRBS1_HUMAN Reviewed; 1292 AA.
AC Q9BX66; A0AED4; A6NEK3; A6NID8; A6NJS4; A7MD40; D3DR42; O43857;
read moreAC Q5T923; Q5T924; Q5T927; Q5T928; Q5T929; Q5T930; Q5T931; Q5T932;
AC Q7LBE5; Q8IVK0; Q8IVQ4; Q96KF3; Q96KF4; Q9BX64; Q9BX65; Q9P2Q0;
AC Q9UFT2; Q9UHN7; Q9Y338;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Sorbin and SH3 domain-containing protein 1;
DE AltName: Full=Ponsin;
DE AltName: Full=SH3 domain protein 5;
DE AltName: Full=SH3P12;
DE AltName: Full=c-Cbl-associated protein;
DE Short=CAP;
GN Name=SORBS1; Synonyms=KIAA0894, KIAA1296, SH3D5;
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] (ISOFORMS 1; 2; 3 AND 4), TISSUE
RP SPECIFICITY, INTERACTION WITH ABL1 AND INSULIN RECEPTOR, AND VARIANT
RP PRO-61.
RC TISSUE=Liver, and Skeletal muscle;
RX PubMed=11374898; DOI=10.1006/geno.2001.6541;
RA Lin W.-H., Huang C.-J., Liu M.-W., Chang H.-M., Chen Y.-J., Tai T.-Y.,
RA Chuang L.-M.;
RT "Cloning, mapping, and characterization of the human sorbin and SH3
RT domain containing 1 (SORBS1) gene: a protein associated with c-Abl
RT during insulin signaling in the hepatoma cell line Hep3B.";
RL Genomics 74:12-20(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), SUBCELLULAR LOCATION,
RP INTERACTION WITH SCA7, AND VARIANT PRO-61.
RC TISSUE=Retina;
RX PubMed=11371513; DOI=10.1093/hmg/10.11.1201;
RA Lebre A.-S., Jamot L., Takahashi J., Spassky N., Leprince C.,
RA Ravise N., Zander C., Fujigasaki H., Kussel-Andermann P.,
RA Duyckaerts C., Camonis J.H., Brice A.;
RT "Ataxin-7 interacts with a Cbl-associated protein that it recruits
RT into neuronal intranuclear inclusions.";
RL Hum. Mol. Genet. 10:1201-1213(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND VARIANTS PRO-61; TRP-74
RP AND ALA-237.
RC TISSUE=Skeletal muscle;
RX PubMed=11532984; DOI=10.1093/hmg/10.17.1753;
RA Lin W.-H., Chiu K.C., Chang H.-M., Lee K.C., Tai T.-Y., Chuang L.-M.;
RT "Molecular scanning of the human sorbin and SH3-domain-containing-1
RT (SORBS1) gene: positive association of the T228A polymorphism with
RT obesity and type 2 diabetes.";
RL Hum. Mol. Genet. 10:1753-1760(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), INTERACTION WITH INPPL1, AND
RP VARIANT PRO-61.
RC TISSUE=Brain;
RX PubMed=12504111; DOI=10.1016/S0006-291X(02)02894-2;
RA Vandenbroere I., Paternotte N., Dumont J.E., Erneux C., Pirson I.;
RT "The c-Cbl-associated protein and c-Cbl are two new partners of the
RT SH2-containing inositol polyphosphate 5-phosphatase SHIP2.";
RL Biochem. Biophys. Res. Commun. 300:494-500(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11), INTERACTION WITH PXN, X-RAY
RP CRYSTALLOGRAPHY (0.83 ANGSTROMS) OF 870-930 IN COMPLEX WITH PXN
RP PEPTIDE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT PRO-61.
RC TISSUE=Skeletal muscle;
RX PubMed=17462669; DOI=10.1016/j.jmb.2007.03.050;
RA Gehmlich K., Pinotsis N., Hayess K., van der Ven P.F., Milting H.,
RA El Banayosy A., Korfer R., Wilmanns M., Ehler E., Furst D.O.;
RT "Paxillin and ponsin interact in nascent costameres of muscle cells.";
RL J. Mol. Biol. 369:665-682(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9), AND VARIANT
RP PRO-61.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10), AND VARIANT
RP PRO-61.
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 9), AND VARIANT
RP PRO-61.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 752-888.
RC TISSUE=Placenta;
RA Hachiya T., Kobayasi A., Touji S., Tamai K.;
RT "A Fas-ligand associated factor 2, FLAF2, potentiates Fas-ligand
RT stability.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86; SER-89; SER-472;
RP SER-665; THR-862 AND SER-945, PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-478 AND SER-735 (ISOFORM 10), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-1213 (ISOFORM 12), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-346 AND SER-603 (ISOFORM 4), PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-923 (ISOFORM 5), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-765 (ISOFORM 6), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-469 (ISOFORM 7), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-730 (ISOFORM 8), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-387 AND SER-700 (ISOFORM 9), AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 870-930.
RX PubMed=17784760; DOI=10.1021/ja073846c;
RA Margiolaki I., Wright J.P., Wilmanns M., Fitch A.N., Pinotsis N.;
RT "Second SH3 domain of ponsin solved from powder diffraction.";
RL J. Am. Chem. Soc. 129:11865-11871(2007).
RN [17]
RP STRUCTURE BY NMR OF 796-926.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of SH3 domains of human Sorbin and SH3 domain-
RT containing protein 1.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [18]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-195.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Plays a role in tyrosine phosphorylation of CBL by
CC linking CBL to the insulin receptor. Required for insulin-
CC stimulated glucose transport. Involved in formation of actin
CC stress fibers and focal adhesions (By similarity).
CC -!- SUBUNIT: Interacts (via third SH3 domain) with the Ten-1 ICD form
CC of TENM1; the interaction induces the translocation of SORBS1 to
CC the nucleus (By similarity). Interacts with the long isoform of
CC MLLT4/afadin and with VCL. MLLT4 and VCL bind to SORBS1 in a
CC competitive manner and do not form a ternary complex. Interacts
CC with ABL1, CBL, CBLB and INPPL1/SHIP2 through the third SH3
CC domain. Interaction with ABL1 occurs only after insulin
CC stimulation while this has no effect on the interaction with
CC INPPL1. Interacts with the insulin receptor but dissociates from
CC it following insulin stimulation. Also interacts with SCA7,
CC PTK2/FAK1 and flotillin. Interacts (via SH3 domain 2) with PXN.
CC -!- INTERACTION:
CC P00519:ABL1; NbExp=2; IntAct=EBI-433642, EBI-375543;
CC O15265:ATXN7; NbExp=15; IntAct=EBI-433642, EBI-708350;
CC P39052:Dnm2 (xeno); NbExp=5; IntAct=EBI-433642, EBI-349613;
CC O15357:INPPL1; NbExp=5; IntAct=EBI-433642, EBI-1384248;
CC Q13177:PAK2; NbExp=2; IntAct=EBI-433642, EBI-1045887;
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction. Cell
CC membrane. Cytoplasm, cytoskeleton. Cell junction, focal adhesion.
CC Nucleus (By similarity). Nucleus matrix (By similarity).
CC Note=Colocalizes with the Ten-1 ICD form of TENM1 in the nucleus
CC (By similarity). Colocalizes with actin stress fibers. Also
CC detected at the plasma membrane and in neuronal intranuclear
CC inclusions. Colocalized with PXN at focal adhesions during
CC myogenic differentiation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=12;
CC Name=1;
CC IsoId=Q9BX66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BX66-2; Sequence=VSP_050902, VSP_050910;
CC Note=Ref.1 (AAK37564) sequence is in conflict in positions:
CC 435:K->E, 452-455:AHCS->SRCG, 463:N->D;
CC Name=3;
CC IsoId=Q9BX66-3; Sequence=VSP_050898, VSP_050900, VSP_050906,
CC VSP_050912, VSP_050913;
CC Name=4;
CC IsoId=Q9BX66-4; Sequence=VSP_050895, VSP_050896, VSP_050899,
CC VSP_050900, VSP_050903, VSP_050907,
CC VSP_050911;
CC Note=Contains a phosphoserine at position 346. Contains a
CC phosphoserine at position 603;
CC Name=5;
CC IsoId=Q9BX66-5; Sequence=VSP_050896, VSP_050901, VSP_050911;
CC Note=Contains a phosphoserine at position 923;
CC Name=6;
CC IsoId=Q9BX66-6; Sequence=VSP_050896, VSP_050899, VSP_050905,
CC VSP_050911;
CC Note=Contains a phosphoserine at position 765;
CC Name=7;
CC IsoId=Q9BX66-7; Sequence=VSP_050895, VSP_050896, VSP_050900,
CC VSP_050903, VSP_050908, VSP_050909;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 469;
CC Name=8;
CC IsoId=Q9BX66-8; Sequence=VSP_050895, VSP_050899, VSP_050900,
CC VSP_050904, VSP_050911;
CC Note=Contains a phosphoserine at position 730;
CC Name=9;
CC IsoId=Q9BX66-9; Sequence=VSP_050899, VSP_050900, VSP_050903,
CC VSP_050911;
CC Note=Contains a phosphoserine at position 387. Contains a
CC phosphoserine at position 700;
CC Name=10;
CC IsoId=Q9BX66-10; Sequence=VSP_050895, VSP_050900, VSP_050903,
CC VSP_050907, VSP_050911;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 478. Contains a phosphoserine at
CC position 735;
CC Name=11;
CC IsoId=Q9BX66-11; Sequence=VSP_050900, VSP_039210;
CC Name=12;
CC IsoId=Q9BX66-12; Sequence=VSP_050895, VSP_050899, VSP_041193,
CC VSP_050900, VSP_050904, VSP_041194,
CC VSP_050911;
CC Note=No experimental confirmation available. Derived from mouse
CC ortholog data. Contains a phosphoserine at position 1213;
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle (at protein
CC level). Widely expressed with highest levels in heart and skeletal
CC muscle.
CC -!- PTM: O-glycosylated (By similarity).
CC -!- SIMILARITY: Contains 3 SH3 domains.
CC -!- SIMILARITY: Contains 1 SoHo domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB93496.1; Type=Frameshift; Positions=861, 867, 885;
CC Sequence=BAA92534.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AF136380; AAD27647.1; -; mRNA.
DR EMBL; AF356525; AAK37563.1; -; mRNA.
DR EMBL; AF356526; AAK37564.1; -; mRNA.
DR EMBL; AF356527; AAK37565.1; -; mRNA.
DR EMBL; AF330623; AAK57479.1; -; mRNA.
DR EMBL; AF330624; AAK57480.1; -; mRNA.
DR EMBL; AF136381; AAF22175.1; -; mRNA.
DR EMBL; AJ489942; CAD34588.1; -; mRNA.
DR EMBL; AM260536; CAJ97431.1; -; mRNA.
DR EMBL; AB037717; BAA92534.1; ALT_INIT; mRNA.
DR EMBL; AL117472; CAB55947.1; -; mRNA.
DR EMBL; AL158165; CAI14378.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14379.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14380.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14381.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14382.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14383.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14384.1; -; Genomic_DNA.
DR EMBL; AL158165; CAI14385.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49999.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW50007.1; -; Genomic_DNA.
DR EMBL; BC042612; AAH42612.1; -; mRNA.
DR EMBL; BC152463; AAI52464.1; -; mRNA.
DR EMBL; U70668; AAB93496.1; ALT_FRAME; mRNA.
DR PIR; T17257; T17257.
DR RefSeq; NP_001030126.1; NM_001034954.1.
DR RefSeq; NP_001030127.1; NM_001034955.1.
DR RefSeq; NP_001030128.1; NM_001034956.1.
DR RefSeq; NP_001030129.1; NM_001034957.1.
DR RefSeq; NP_006425.2; NM_006434.2.
DR RefSeq; NP_056200.1; NM_015385.2.
DR RefSeq; NP_079267.1; NM_024991.1.
DR RefSeq; XP_005269484.1; XM_005269427.1.
DR RefSeq; XP_005269490.1; XM_005269433.1.
DR RefSeq; XP_005269493.1; XM_005269436.1.
DR RefSeq; XP_005269495.1; XM_005269438.1.
DR UniGene; Hs.38621; -.
DR PDB; 2DL3; NMR; -; A=791-850.
DR PDB; 2ECZ; NMR; -; A=870-926.
DR PDB; 2LJ0; NMR; -; A=1228-1292.
DR PDB; 2LJ1; NMR; -; A=1228-1291.
DR PDB; 2O2W; X-ray; 2.27 A; A=870-930.
DR PDB; 2O31; X-ray; 1.50 A; A=870-930.
DR PDB; 2O9S; X-ray; 0.83 A; A=870-930.
DR PDB; 2O9V; X-ray; 1.63 A; A=870-930.
DR PDBsum; 2DL3; -.
DR PDBsum; 2ECZ; -.
DR PDBsum; 2LJ0; -.
DR PDBsum; 2LJ1; -.
DR PDBsum; 2O2W; -.
DR PDBsum; 2O31; -.
DR PDBsum; 2O9S; -.
DR PDBsum; 2O9V; -.
DR ProteinModelPortal; Q9BX66; -.
DR SMR; Q9BX66; 791-930, 1228-1292.
DR IntAct; Q9BX66; 24.
DR MINT; MINT-2792261; -.
DR PhosphoSite; Q9BX66; -.
DR DMDM; 215273913; -.
DR PaxDb; Q9BX66; -.
DR PRIDE; Q9BX66; -.
DR DNASU; 10580; -.
DR Ensembl; ENST00000277982; ENSP00000277982; ENSG00000095637.
DR Ensembl; ENST00000306402; ENSP00000302556; ENSG00000095637.
DR Ensembl; ENST00000347291; ENSP00000277985; ENSG00000095637.
DR Ensembl; ENST00000353505; ENSP00000343998; ENSG00000095637.
DR Ensembl; ENST00000354106; ENSP00000277984; ENSG00000095637.
DR Ensembl; ENST00000361941; ENSP00000355136; ENSG00000095637.
DR Ensembl; ENST00000371227; ENSP00000360271; ENSG00000095637.
DR Ensembl; ENST00000371239; ENSP00000360283; ENSG00000095637.
DR Ensembl; ENST00000371241; ENSP00000360285; ENSG00000095637.
DR Ensembl; ENST00000371245; ENSP00000360291; ENSG00000095637.
DR Ensembl; ENST00000371246; ENSP00000360292; ENSG00000095637.
DR Ensembl; ENST00000371247; ENSP00000360293; ENSG00000095637.
DR Ensembl; ENST00000371249; ENSP00000360295; ENSG00000095637.
DR Ensembl; ENST00000393949; ENSP00000377521; ENSG00000095637.
DR Ensembl; ENST00000607232; ENSP00000475901; ENSG00000095637.
DR GeneID; 10580; -.
DR KEGG; hsa:10580; -.
DR UCSC; uc001kkp.3; human.
DR CTD; 10580; -.
DR GeneCards; GC10M097061; -.
DR HGNC; HGNC:14565; SORBS1.
DR HPA; HPA027559; -.
DR HPA; HPA036994; -.
DR MIM; 605264; gene.
DR neXtProt; NX_Q9BX66; -.
DR PharmGKB; PA37899; -.
DR eggNOG; NOG256936; -.
DR HOVERGEN; HBG053053; -.
DR InParanoid; Q9BX66; -.
DR KO; K06086; -.
DR OMA; ITSEWIS; -.
DR OrthoDB; EOG75XGKP; -.
DR PhylomeDB; Q9BX66; -.
DR Reactome; REACT_17044; Muscle contraction.
DR SignaLink; Q9BX66; -.
DR ChiTaRS; SORBS1; human.
DR EvolutionaryTrace; Q9BX66; -.
DR GeneWiki; SORBS1; -.
DR GenomeRNAi; 10580; -.
DR NextBio; 40165; -.
DR PRO; PR:Q9BX66; -.
DR ArrayExpress; Q9BX66; -.
DR Bgee; Q9BX66; -.
DR Genevestigator; Q9BX66; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; ISS:BHF-UCL.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001725; C:stress fiber; ISS:UniProtKB.
DR GO; GO:0005915; C:zonula adherens; TAS:ProtInc.
DR GO; GO:0003779; F:actin binding; TAS:ProtInc.
DR GO; GO:0005158; F:insulin receptor binding; IDA:UniProtKB.
DR GO; GO:0005070; F:SH3/SH2 adaptor activity; ISS:BHF-UCL.
DR GO; GO:0048041; P:focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0015758; P:glucose transport; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:BHF-UCL.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0043149; P:stress fiber assembly; ISS:UniProtKB.
DR InterPro; IPR028506; CAP/ponsin.
DR InterPro; IPR011511; SH3_2.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR003127; Sorb.
DR PANTHER; PTHR10661:SF4; PTHR10661:SF4; 1.
DR Pfam; PF07653; SH3_2; 1.
DR Pfam; PF02208; Sorb; 1.
DR SMART; SM00326; SH3; 3.
DR SMART; SM00459; Sorb; 1.
DR SUPFAM; SSF50044; SSF50044; 3.
DR PROSITE; PS50002; SH3; 3.
DR PROSITE; PS50831; SOHO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Complete proteome; Cytoplasm; Cytoskeleton; Glycoprotein; Membrane;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW SH3 domain; Transport.
FT CHAIN 1 1292 Sorbin and SH3 domain-containing protein
FT 1.
FT /FTId=PRO_0000072185.
FT DOMAIN 366 469 SoHo.
FT DOMAIN 793 852 SH3 1.
FT DOMAIN 867 928 SH3 2.
FT DOMAIN 1231 1292 SH3 3.
FT MOD_RES 86 86 Phosphoserine.
FT MOD_RES 89 89 Phosphoserine.
FT MOD_RES 369 369 Phosphoserine (By similarity).
FT MOD_RES 472 472 Phosphoserine.
FT MOD_RES 481 481 Phosphoserine.
FT MOD_RES 536 536 Phosphotyrosine; by ABL1 (By similarity).
FT MOD_RES 654 654 Phosphotyrosine; by ABL1 (By similarity).
FT MOD_RES 665 665 Phosphoserine.
FT MOD_RES 862 862 Phosphothreonine.
FT MOD_RES 945 945 Phosphoserine.
FT MOD_RES 1240 1240 Phosphotyrosine; by ABL1 (By similarity).
FT VAR_SEQ 26 57 Missing (in isoform 4, isoform 7, isoform
FT 8, isoform 10 and isoform 12).
FT /FTId=VSP_050895.
FT VAR_SEQ 101 109 Missing (in isoform 4, isoform 5, isoform
FT 6 and isoform 7).
FT /FTId=VSP_050896.
FT VAR_SEQ 147 215 Missing (in isoform 3).
FT /FTId=VSP_050898.
FT VAR_SEQ 148 270 Missing (in isoform 4, isoform 6, isoform
FT 8, isoform 9 and isoform 12).
FT /FTId=VSP_050899.
FT VAR_SEQ 319 328 Missing (in isoform 12).
FT /FTId=VSP_041193.
FT VAR_SEQ 408 453 Missing (in isoform 3, isoform 4, isoform
FT 7, isoform 8, isoform 9, isoform 10,
FT isoform 11 and isoform 12).
FT /FTId=VSP_050900.
FT VAR_SEQ 431 451 Missing (in isoform 5).
FT /FTId=VSP_050901.
FT VAR_SEQ 434 453 DNPYTPTYQFPASTPSPKSE -> TKSCSVMSPRLECSGTV
FT IAHCSLKLLDSSNPPTSASQVAGTA (in isoform 2).
FT /FTId=VSP_050902.
FT VAR_SEQ 552 635 Missing (in isoform 4, isoform 7, isoform
FT 9 and isoform 10).
FT /FTId=VSP_050903.
FT VAR_SEQ 580 635 Missing (in isoform 6).
FT /FTId=VSP_050905.
FT VAR_SEQ 580 601 Missing (in isoform 8 and isoform 12).
FT /FTId=VSP_050904.
FT VAR_SEQ 602 635 Missing (in isoform 3).
FT /FTId=VSP_050906.
FT VAR_SEQ 709 709 K -> KVDRKGGNAHMISSSSVHSRTFNTSNALGPVCKHKK
FT PLSAAKACISEILPSKFKPRLSAPSALLQEQKSILLPSEKA
FT QSCENLCVSGSLNDSKRGLPLQVGGSIENLLMRSRRDYDSK
FT SSSTMSLQEYSTSGRRPCPLSRKAGMQFTMLYRDMHQINRS
FT GLFLGSISSSSSVRDLASHFEKSSLALSRGELGPSQEGSEH
FT IPKHTVSSRITAFEQLIQRSRSMPSLDLSGRLSKSPTPVLS
FT RGSLTSARSAESLLESTKLHPKEMDGMNSSGVYASPTCSNM
FT AHHALSFRGLVPSEPLSTCSDDVDRCSNISTDSREGSGGSV
FT HGDFPKHRLNKCKGTCPASYTRFTTIRKHEQQQTSRQPEWR
FT LDARGDKSTLLRNIYLMSPLPFRLKKPLHHHPRQPSPGDSS
FT GLLVGQKPDLPSQPHQDQPPSGGKPVVPTRLSSRHTMARLS
FT RSSEPSQERPTALEDYPRAINNGNSVPYSDHSLDRNNNPQS
FT ELAPSRG (in isoform 12).
FT /FTId=VSP_041194.
FT VAR_SEQ 738 793 Missing (in isoform 4 and isoform 10).
FT /FTId=VSP_050907.
FT VAR_SEQ 795 799 MRPAR -> KYDWA (in isoform 7).
FT /FTId=VSP_050908.
FT VAR_SEQ 800 1292 Missing (in isoform 7).
FT /FTId=VSP_050909.
FT VAR_SEQ 955 1212 Missing (in isoform 4, isoform 5, isoform
FT 6, isoform 8, isoform 9, isoform 10 and
FT isoform 12).
FT /FTId=VSP_050911.
FT VAR_SEQ 955 1117 Missing (in isoform 2).
FT /FTId=VSP_050910.
FT VAR_SEQ 956 975 FSSHSKLITPAPSSLPHSRR -> LSHHSLRAGPDLTESEK
FT SYV (in isoform 3).
FT /FTId=VSP_050912.
FT VAR_SEQ 976 1213 Missing (in isoform 3).
FT /FTId=VSP_050913.
FT VAR_SEQ 1213 1213 Q -> QLSHHSLRAGPDLTESEKSYV (in isoform
FT 11).
FT /FTId=VSP_039210.
FT VARIANT 61 61 L -> P (in dbSNP:rs943542).
FT /FTId=VAR_047652.
FT VARIANT 74 74 R -> W.
FT /FTId=VAR_019653.
FT VARIANT 175 175 G -> V (in dbSNP:rs7081076).
FT /FTId=VAR_047653.
FT VARIANT 195 195 T -> A (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035661.
FT VARIANT 237 237 T -> A (has a protective role in both
FT obesity and diabetes; dbSNP:rs2281939).
FT /FTId=VAR_019654.
FT VARIANT 485 485 Y -> C (in dbSNP:rs35808802).
FT /FTId=VAR_047654.
FT CONFLICT 9 9 S -> P (in Ref. 5; CAJ97431).
FT CONFLICT 18 18 P -> S (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 110 110 D -> G (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 113 113 R -> K (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 131 131 A -> V (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 134 134 Y -> S (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 226 228 RAS -> SAC (in Ref. 3; AAF22175).
FT CONFLICT 264 264 T -> P (in Ref. 3; AAF22175).
FT CONFLICT 292 295 PSVS -> SSEC (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 481 481 S -> R (in Ref. 3; AAF22175).
FT CONFLICT 489 489 E -> V (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 607 607 D -> E (in Ref. 3; AAF22175).
FT CONFLICT 610 610 L -> F (in Ref. 3; AAF22175).
FT CONFLICT 644 644 E -> G (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 679 679 R -> S (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 690 690 D -> V (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 694 694 Q -> R (in Ref. 5; CAJ97431).
FT CONFLICT 695 695 G -> D (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 710 710 D -> N (in Ref. 1; AAD27647 and 3;
FT AAF22175).
FT CONFLICT 1156 1156 V -> G (in Ref. 1; AAK37563/AAK37564).
FT STRAND 796 802
FT STRAND 819 824
FT STRAND 830 834
FT STRAND 839 843
FT TURN 844 846
FT STRAND 847 849
FT STRAND 870 874
FT STRAND 893 899
FT STRAND 901 908
FT TURN 910 912
FT STRAND 915 919
FT HELIX 920 922
FT STRAND 923 927
FT STRAND 1230 1233
FT STRAND 1235 1240
FT STRAND 1257 1263
FT STRAND 1267 1273
FT TURN 1274 1276
FT STRAND 1279 1283
FT STRAND 1286 1289
SQ SEQUENCE 1292 AA; 142513 MW; 70DA4169B6D82F06 CRC64;
MSSECDGGSK AVMNGLAPGS NGQDKATADP LRARSISAVK IIPVKTVKNA SGLVLPTDMD
LTKICTGKGA VTLRASSSYR ETPSSSPASP QETRQHESKP GLEPEPSSAD EWRLSSSADA
NGNAQPSSLA AKGYRSVHPN LPSDKSQDAT SSSAAQPEVI VVPLYLVNTD RGQEGTARPP
TPLGPLGCVP TIPATASAAS PLTFPTLDDF IPPHLQRWPH HSQPARASGS FAPISQTPPS
FSPPPPLVPP APEDLRRVSE PDLTGAVSST DSSPLLNEVS SSLIGTDSQA FPSVSKPSSA
YPSTTIVNPT IVLLQHNREQ QKRLSSLSDP VSERRVGEQD SAPTQEKPTS PGKAIEKRAK
DDSRRVVKST QDLSDVSMDE VGIPLRNTER SKDWYKTMFK QIHKLNRDTP EENPYFPTYK
FPELPEIQQT SEEDNPYTPT YQFPASTPSP KSEDDDSDLY SPRYSFSEDT KSPLSVPRSK
SEMSYIDGEK VVKRSATLPL PARSSSLKSS SERNDWEPPD KKVDTRKYRA EPKSIYEYQP
GKSSVLTNEK MSRDISPEEI DLKNEPWYKF FSELEFGKPP PKKIWDYTPG DCSILPREDR
KTNLDKDLSL CQTELEADLE KMETLNKAPS ANVPQSSAIS PTPEISSETP GYIYSSNFHA
VKRESDGAPG DLTSLENERQ IYKSVLEGGD IPLQGLSGLK RPSSSASTKD SESPRHFIPA
DYLESTEEFI RRRHDDKEKL LADQRRLKRE QEEADIAARR HTGVIPTHHQ FITNERFGDL
LNIDDTAKRK SGSEMRPARA KFDFKAQTLK ELPLQKGDIV YIYKQIDQNW YEGEHHGRVG
IFPRTYIELL PPAEKAQPKK LTPVQVLEYG EAIAKFNFNG DTQVEMSFRK GERITLLRQV
DENWYEGRIP GTSRQGIFPI TYVDVIKRPL VKNPVDYMDL PFSSSPSRSA TASPQFSSHS
KLITPAPSSL PHSRRALSPE MHAVTSEWIS LTVGVPGRRS LALTPPLPPL PEASIYNTDH
LALSPRASPS LSLSLPHLSW SDRPTPRSVA SPLALPSPHK TYSLAPTSQA SLHMNGDGGV
HTPSSGIHQD SFLQLPLGSS DSVISQLSDA FSSQSKRQPW REESGQYERK AERGAGERGP
GGPKISKKSC LKPSDVVRCL STEQRLSDLN TPEESRPGKP LGSAFPGSEA EQTERHRGGE
QAGRKAARRG GSQQPQAQQR RVTPDRSQTS QDLFSYQALY SYIPQNDDEL ELRDGDIVDV
MEKCDDGWFV GTSRRTKQFG TFPGNYVKPL YL
//
MIM
605264
*RECORD*
*FIELD* NO
605264
*FIELD* TI
*605264 SORBIN AND SH3-DOMAINS CONTAINING 1; SORBS1
;;SH3 DOMAIN PROTEIN 5; SH3D5;;
read moreCBL-ASSOCIATED PROTEIN; CAP;;
SH3 DOMAIN-CONTAINING PROTEIN 12; SH3P12;;
PONSIN;;
SORB1
*FIELD* TX
CLONING
The protein product of the CBL protooncogene (165360) is prominently
tyrosine phosphorylated in response to insulin (176730) in 3T3-L1
adipocytes but not in 3T3-L1 fibroblasts. After insulin-dependent
tyrosine phosphorylation, CBL specifically associates with endogenous
CRK (164762) and FYN (137025). These results suggest a role for
tyrosine-phosphorylated CBL in adipocyte activation by insulin. Ribon et
al. (1998) used full-length CBL as a target protein to screen a fully
differentiated 3T3-L1 adipocyte cDNA library using the yeast 2-hybrid
system. They isolated cDNAs encompassing the entire coding region of Cap
(CBL-associated protein) from a mouse embryo cDNA expression library by
using a functional screen with a defined SH3 ligand peptide. The unique
structure of Cap includes 3 adjacent Src homology-3 (SH3) domains in the
C terminus and a region showing significant sequence similarity with the
peptide hormone sorbin. Both Cap mRNA and proteins were expressed
predominantly in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. By
Northern blot analysis of mouse tissues, Cap expression was detected in
greatest abundance in heart, liver, skeletal muscle, and kidney; lesser
amounts were detected in brain and lung, and expression in spleen and
testis was not detected.
Scott (2000) considered the mouse Cap protein to be the probable
ortholog of human SH3P12 (GenBank GENBANK AF136380).
Spinocerebellar ataxia-7 (SCA7; 164500) is a neurodegenerative disease
caused by expansion of a CAG repeat in the coding region of the SCA7
gene. Ataxin-7, encoded by the SCA7 gene, is a protein expressed in many
tissues, including the CNS. Lebre et al. (2001) used a 2-hybrid approach
to screen a human retina cDNA library for ataxin-7-binding proteins and
isolated R85, a splice variant of SH3P12. SH3P12 gene products were
expressed in Purkinje cells in the cerebellum.
GENE FUNCTION
Ribon et al. (1998) found that Cap associated with CBL in 3T3-L1
adipocytes independently of insulin stimulation in vivo and in vitro in
an SH3 domain-mediated manner. Furthermore, Ribon et al. (1998) detected
the association of Cap with insulin receptor (147670). Insulin
stimulation resulted in the dissociation of Cap from the insulin
receptor. Taken together, Ribon et al. (1998) concluded that CAP
represents a novel CBL-binding protein in adipocytes likely to
participate in insulin signaling.
Insulin stimulates the transport of glucose into fat and muscle cells
and initiates its actions by binding to its tyrosine kinase receptor,
leading to the phosphorylation of intracellular substrates. One such
substrate is the CBL protooncogene product. CBL is recruited to the
insulin receptor by interaction with the adaptor protein CAP, through 1
of 3 adjacent SH3 domains in the C terminus of CAP. Upon phosphorylation
of CBL, the CAP-CBL complex dissociates from the insulin receptor and
moves to a caveolin (see 601047)-enriched triton-insoluble membrane
fraction (Mastick et al., 1995). To identify a molecular mechanism
underlying this subcellular redistribution, Baumann et al. (2000)
screened a yeast 2-hybrid library using the N-terminal region of CAP and
identified the caveolar protein flotillin (131560). Flotillin forms a
ternary complex with CAP and CBL, directing the localization of the
CAP-CBL complex to a lipid raft subdomain of the plasma membrane.
Expression of the N-terminal domain of CAP in 3T3-L1 adipocytes blocks
the stimulation of glucose transport by insulin, without affecting
signaling events that depend on phosphatidylinositol-3-OH kinase (see
602838). Thus, localization of the CBL-CAP complex to lipid rafts
generates a pathway that is crucial in the regulation of glucose uptake.
The stimulation of glucose uptake by insulin in muscle and adipose
tissue requires translocation of the GLUT4 glucose transporter (138190)
from intracellular storage sites to the cell surface. Activation of
phosphatidylinositol-3-OH kinase (PI3K) is required for this trafficking
event, but it is not sufficient to produce GLUT4 translocation. Ribon et
al. (1998) and Baumann et al. (2000) described a pathway involving the
insulin-stimulated tyrosine phosphorylation of CBL (165360), which is
recruited to the insulin receptor (147670) by the adaptor protein CAP.
On phosphorylation, CBL is translocated to lipid rafts. Blocking this
step completely inhibits the stimulation of GLUT4 translocation by
insulin. Chiang et al. (2001) showed that phosphorylated CBL recruits
the CRK2-C3G (164762, 600303) complex to lipid rafts, where C3G
specifically activates the small GTP-binding protein TC10 (605857). This
process is independent of PI3K, but requires the translocation of CBL,
CRK, and C3G to the lipid raft. The activation of TC10 is essential for
insulin-stimulated glucose uptake and GLUT4 translocation. The TC10
pathway functions in parallel with PI3K to stimulate fully GLUT4
translocation in response to insulin.
Lebre et al. (2001) confirmed the interactions between ataxin-7 and
SH3P12 gene products by pull-down and coimmunoprecipitation. Ataxin-7
colocalized with full-length R85 in cotransfected COS-7 cells and with
one of the SH3P12 gene products in neuronal intranuclear inclusions in
brain from a SCA7 patient. The authors proposed that this interaction is
part of a physiologic pathway related to the function or turnover of
ataxin-7.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SORBS1
gene to chromosome 10 (TMAP stSG35884). Grupe et al. (2006) demonstrated
close situation of the SORBS1 gene to the ENTPD1 gene (601752) on
chromosome 10q24.
MOLECULAR GENETICS
Lin et al. (2001) identified 14 single-nucleotide polymorphisms (SNPs)
in the human SH3P12 gene, which they called SORBS1. Studies in 202
nonobese, 113 obese, and 455 subjects with type II diabetes (125853)
revealed that the alanine allele of a T228A polymorphism in exon 7
exerted a protective role for both obesity (601665) (relative risk,
0.466; 95% CI, 0.265 to 0.821) and diabetes (relative risk, 0.668; 95%
CI, 0.472 to 0.945). Neither allele of the R74W polymorphism was
associated with either obesity or diabetes. The authors suggested that
the SH3P12 gene may play an important role in the pathogenesis of human
disorders with insulin resistance.
Grupe et al. (2006) reported evidence suggesting genetic association
between SNP dbSNP rs498055 on 10q24, upstream of the SORBS1 gene and
located near a putative homolog of ribosomal protein S3a (RPS3A;
180478), and risk of late-onset Alzheimer disease (AD6; 605526) in 4 of
6 independent case-control samples. However, Bertram et al. (2006) could
not corroborate the association with Alzheimer disease in 2 independent
family samples. Analysis of 3 family-based and 1 case-control datasets
by Liang et al. (2008) showed that dbSNP rs498055 was not associated
with an increased risk of late-onset Alzheimer disease.
ANIMAL MODEL
Lesniewski et al. (2007) generated Sorbs1-null mice and found that they
were protected against high-fat diet-induced insulin resistance and had
reduced tissue markers of inflammation. Using bone marrow
transplantation to generate functional Sorbs1-null macrophages, the
authors demonstrated that the insulin-sensitive phenotype could be
transferred to wildtype mice. Lesniewski et al. (2007) concluded that
macrophages are an important cell type for the induction of insulin
resistance and that Sorbs1 has a modulatory role in that function.
*FIELD* RF
1. Baumann, C. A.; Ribon, V.; Kanzaki, M.; Thurmond, D. C.; Mora,
S.; Shigematsu, S.; Bickel, P. E.; Pessin, J. E.; Saltiel, A. R.:
CAP defines a second signalling pathway required for insulin-stimulated
glucose transport. Nature 407: 202-207, 2000.
2. Bertram, L.; Hsiao, M.; Lange, C.; Blacker, D.; Tanzi, R. E.:
Single-nucleotide polymorphism rs498055 on chromosome 10q24 is not
associated with Alzheimer disease in two independent family samples.
(Letter) Am. J. Hum. Genet. 79: 180-183, 2006.
3. Chiang, S.-H.; Baumann, C. A.; Kanzaki, M.; Thurmond, D. C.; Watson,
R. T.; Neudauer, C. L.; Macara, I. G.; Pessin, J. E.; Saltiel, A.
R.: Insulin-stimulated GLUT4 translocation requires the CAP-dependent
activation of TC10. Nature 410: 944-948, 2001.
4. Grupe, A.; Li, Y.; Rowland, C.; Nowotny, P.; Hinrichs, A. L.; Smemo,
S.; Kauwe, J. S. K.; Maxwell, T. J.; Cherny, S.; Doil, L.; Tacey,
K.; van Luchene, R.; and 23 others: A scan of chromosome 10 identifies
a novel locus showing strong association with late-onset Alzheimer
disease. Am. J. Hum. Genet. 78: 78-88, 2006.
5. Lebre, A.-S.; Jamot, L.; Takahashi, J.; Spasskey, N.; Leprince,
C.; Ravise, N.; Zander, C.; Fujigasaki, H.; Kussel-Andermann, P.;
Duyckaerts, C.; Camonis, J. H.; Brice, A.: Ataxin-7 interacts with
a Cbl-associated protein that it recruits into neuronal intranuclear
inclusions. Hum. Molec. Genet. 10: 1201-1213, 2001.
6. Lesniewski, L. A.; Hosch, S. E.; Neels, J. G.; de Luca, C.; Pashmforoush,
M.; Lumeng, C. N.; Chiang, S.-H.; Scadeng, M.; Saltiel, A. R.; Olefsky,
J. M.: Bone marrow-specific Cap gene deletion protects against high-fat
diet-induced insulin resistance. Nature Med. 13: 455-462, 2007.
7. Liang, X.; Schnetz-Boutaud, N.; Bartlett, J.; Allen, M. J.; Gwirtsman,
H.; Schmechel, D. E.; Carney, R. M.; Gilbert J. R.; Pericak-Vance,
M. A.; Haines, J. L.: No association between SNP rs498055 on chromosome
10 and late-onset Alzheimer disease in multiple datasets. Ann. Hum.
Genet. 72: 141-144, 2008.
8. Lin, W.-H.; Chiu, K. C.; Chang, H.-M.; Lee, K.-C.; Tai, T.-Y.;
Chuang, L.-M.: Molecular scanning of the human sorbin and SH3-domain-containing-1
(SORBS1) gene: positive association of the T228A polymorphism with
obesity and type 2 diabetes. Hum. Molec. Genet. 10: 1753-1760, 2001.
9. Mastick, C. C.; Brady, M. J.; Saltiel, A. R.: Insulin stimulates
the tyrosine phosphorylation of caveolin. J. Cell Biol. 129: 1523-1531,
1995.
10. Ribon, V.; Printen, J. A.; Hoffman, N. G.; Kay, B. K.; Saltiel,
A. R.: A novel, multifunctional c-Cbl binding protein in insulin
receptor signaling in 3T3-L1 adipocytes. Molec. Cell. Biol. 18:
872-879, 1998.
11. Scott, A. F.: Personal Communication. Baltimore, Md. 9/13/2000.
*FIELD* CN
Joanna S. Amberger - updated: 10/6/2008
Marla J. F. O'Neill - updated: 6/5/2007
Victor A. McKusick - updated: 6/13/2006
Victor A. McKusick - updated: 12/29/2005
Joanna S. Amberger - updated: 7/16/2002
George E. Tiller - updated: 2/5/2002
George E. Tiller - updated: 10/19/2001
Ada Hamosh - updated: 4/16/2001
*FIELD* CD
Ada Hamosh: 9/13/2000
*FIELD* ED
ckniffin: 03/16/2011
alopez: 10/23/2008
carol: 10/7/2008
joanna: 10/6/2008
wwang: 6/7/2007
terry: 6/5/2007
wwang: 2/23/2007
mgross: 11/20/2006
terry: 6/13/2006
terry: 2/3/2006
terry: 12/29/2005
alopez: 11/5/2003
joanna: 7/16/2002
cwells: 2/13/2002
cwells: 2/5/2002
cwells: 10/30/2001
cwells: 10/19/2001
alopez: 4/18/2001
terry: 4/16/2001
alopez: 3/28/2001
alopez: 9/13/2000
*RECORD*
*FIELD* NO
605264
*FIELD* TI
*605264 SORBIN AND SH3-DOMAINS CONTAINING 1; SORBS1
;;SH3 DOMAIN PROTEIN 5; SH3D5;;
read moreCBL-ASSOCIATED PROTEIN; CAP;;
SH3 DOMAIN-CONTAINING PROTEIN 12; SH3P12;;
PONSIN;;
SORB1
*FIELD* TX
CLONING
The protein product of the CBL protooncogene (165360) is prominently
tyrosine phosphorylated in response to insulin (176730) in 3T3-L1
adipocytes but not in 3T3-L1 fibroblasts. After insulin-dependent
tyrosine phosphorylation, CBL specifically associates with endogenous
CRK (164762) and FYN (137025). These results suggest a role for
tyrosine-phosphorylated CBL in adipocyte activation by insulin. Ribon et
al. (1998) used full-length CBL as a target protein to screen a fully
differentiated 3T3-L1 adipocyte cDNA library using the yeast 2-hybrid
system. They isolated cDNAs encompassing the entire coding region of Cap
(CBL-associated protein) from a mouse embryo cDNA expression library by
using a functional screen with a defined SH3 ligand peptide. The unique
structure of Cap includes 3 adjacent Src homology-3 (SH3) domains in the
C terminus and a region showing significant sequence similarity with the
peptide hormone sorbin. Both Cap mRNA and proteins were expressed
predominantly in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. By
Northern blot analysis of mouse tissues, Cap expression was detected in
greatest abundance in heart, liver, skeletal muscle, and kidney; lesser
amounts were detected in brain and lung, and expression in spleen and
testis was not detected.
Scott (2000) considered the mouse Cap protein to be the probable
ortholog of human SH3P12 (GenBank GENBANK AF136380).
Spinocerebellar ataxia-7 (SCA7; 164500) is a neurodegenerative disease
caused by expansion of a CAG repeat in the coding region of the SCA7
gene. Ataxin-7, encoded by the SCA7 gene, is a protein expressed in many
tissues, including the CNS. Lebre et al. (2001) used a 2-hybrid approach
to screen a human retina cDNA library for ataxin-7-binding proteins and
isolated R85, a splice variant of SH3P12. SH3P12 gene products were
expressed in Purkinje cells in the cerebellum.
GENE FUNCTION
Ribon et al. (1998) found that Cap associated with CBL in 3T3-L1
adipocytes independently of insulin stimulation in vivo and in vitro in
an SH3 domain-mediated manner. Furthermore, Ribon et al. (1998) detected
the association of Cap with insulin receptor (147670). Insulin
stimulation resulted in the dissociation of Cap from the insulin
receptor. Taken together, Ribon et al. (1998) concluded that CAP
represents a novel CBL-binding protein in adipocytes likely to
participate in insulin signaling.
Insulin stimulates the transport of glucose into fat and muscle cells
and initiates its actions by binding to its tyrosine kinase receptor,
leading to the phosphorylation of intracellular substrates. One such
substrate is the CBL protooncogene product. CBL is recruited to the
insulin receptor by interaction with the adaptor protein CAP, through 1
of 3 adjacent SH3 domains in the C terminus of CAP. Upon phosphorylation
of CBL, the CAP-CBL complex dissociates from the insulin receptor and
moves to a caveolin (see 601047)-enriched triton-insoluble membrane
fraction (Mastick et al., 1995). To identify a molecular mechanism
underlying this subcellular redistribution, Baumann et al. (2000)
screened a yeast 2-hybrid library using the N-terminal region of CAP and
identified the caveolar protein flotillin (131560). Flotillin forms a
ternary complex with CAP and CBL, directing the localization of the
CAP-CBL complex to a lipid raft subdomain of the plasma membrane.
Expression of the N-terminal domain of CAP in 3T3-L1 adipocytes blocks
the stimulation of glucose transport by insulin, without affecting
signaling events that depend on phosphatidylinositol-3-OH kinase (see
602838). Thus, localization of the CBL-CAP complex to lipid rafts
generates a pathway that is crucial in the regulation of glucose uptake.
The stimulation of glucose uptake by insulin in muscle and adipose
tissue requires translocation of the GLUT4 glucose transporter (138190)
from intracellular storage sites to the cell surface. Activation of
phosphatidylinositol-3-OH kinase (PI3K) is required for this trafficking
event, but it is not sufficient to produce GLUT4 translocation. Ribon et
al. (1998) and Baumann et al. (2000) described a pathway involving the
insulin-stimulated tyrosine phosphorylation of CBL (165360), which is
recruited to the insulin receptor (147670) by the adaptor protein CAP.
On phosphorylation, CBL is translocated to lipid rafts. Blocking this
step completely inhibits the stimulation of GLUT4 translocation by
insulin. Chiang et al. (2001) showed that phosphorylated CBL recruits
the CRK2-C3G (164762, 600303) complex to lipid rafts, where C3G
specifically activates the small GTP-binding protein TC10 (605857). This
process is independent of PI3K, but requires the translocation of CBL,
CRK, and C3G to the lipid raft. The activation of TC10 is essential for
insulin-stimulated glucose uptake and GLUT4 translocation. The TC10
pathway functions in parallel with PI3K to stimulate fully GLUT4
translocation in response to insulin.
Lebre et al. (2001) confirmed the interactions between ataxin-7 and
SH3P12 gene products by pull-down and coimmunoprecipitation. Ataxin-7
colocalized with full-length R85 in cotransfected COS-7 cells and with
one of the SH3P12 gene products in neuronal intranuclear inclusions in
brain from a SCA7 patient. The authors proposed that this interaction is
part of a physiologic pathway related to the function or turnover of
ataxin-7.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SORBS1
gene to chromosome 10 (TMAP stSG35884). Grupe et al. (2006) demonstrated
close situation of the SORBS1 gene to the ENTPD1 gene (601752) on
chromosome 10q24.
MOLECULAR GENETICS
Lin et al. (2001) identified 14 single-nucleotide polymorphisms (SNPs)
in the human SH3P12 gene, which they called SORBS1. Studies in 202
nonobese, 113 obese, and 455 subjects with type II diabetes (125853)
revealed that the alanine allele of a T228A polymorphism in exon 7
exerted a protective role for both obesity (601665) (relative risk,
0.466; 95% CI, 0.265 to 0.821) and diabetes (relative risk, 0.668; 95%
CI, 0.472 to 0.945). Neither allele of the R74W polymorphism was
associated with either obesity or diabetes. The authors suggested that
the SH3P12 gene may play an important role in the pathogenesis of human
disorders with insulin resistance.
Grupe et al. (2006) reported evidence suggesting genetic association
between SNP dbSNP rs498055 on 10q24, upstream of the SORBS1 gene and
located near a putative homolog of ribosomal protein S3a (RPS3A;
180478), and risk of late-onset Alzheimer disease (AD6; 605526) in 4 of
6 independent case-control samples. However, Bertram et al. (2006) could
not corroborate the association with Alzheimer disease in 2 independent
family samples. Analysis of 3 family-based and 1 case-control datasets
by Liang et al. (2008) showed that dbSNP rs498055 was not associated
with an increased risk of late-onset Alzheimer disease.
ANIMAL MODEL
Lesniewski et al. (2007) generated Sorbs1-null mice and found that they
were protected against high-fat diet-induced insulin resistance and had
reduced tissue markers of inflammation. Using bone marrow
transplantation to generate functional Sorbs1-null macrophages, the
authors demonstrated that the insulin-sensitive phenotype could be
transferred to wildtype mice. Lesniewski et al. (2007) concluded that
macrophages are an important cell type for the induction of insulin
resistance and that Sorbs1 has a modulatory role in that function.
*FIELD* RF
1. Baumann, C. A.; Ribon, V.; Kanzaki, M.; Thurmond, D. C.; Mora,
S.; Shigematsu, S.; Bickel, P. E.; Pessin, J. E.; Saltiel, A. R.:
CAP defines a second signalling pathway required for insulin-stimulated
glucose transport. Nature 407: 202-207, 2000.
2. Bertram, L.; Hsiao, M.; Lange, C.; Blacker, D.; Tanzi, R. E.:
Single-nucleotide polymorphism rs498055 on chromosome 10q24 is not
associated with Alzheimer disease in two independent family samples.
(Letter) Am. J. Hum. Genet. 79: 180-183, 2006.
3. Chiang, S.-H.; Baumann, C. A.; Kanzaki, M.; Thurmond, D. C.; Watson,
R. T.; Neudauer, C. L.; Macara, I. G.; Pessin, J. E.; Saltiel, A.
R.: Insulin-stimulated GLUT4 translocation requires the CAP-dependent
activation of TC10. Nature 410: 944-948, 2001.
4. Grupe, A.; Li, Y.; Rowland, C.; Nowotny, P.; Hinrichs, A. L.; Smemo,
S.; Kauwe, J. S. K.; Maxwell, T. J.; Cherny, S.; Doil, L.; Tacey,
K.; van Luchene, R.; and 23 others: A scan of chromosome 10 identifies
a novel locus showing strong association with late-onset Alzheimer
disease. Am. J. Hum. Genet. 78: 78-88, 2006.
5. Lebre, A.-S.; Jamot, L.; Takahashi, J.; Spasskey, N.; Leprince,
C.; Ravise, N.; Zander, C.; Fujigasaki, H.; Kussel-Andermann, P.;
Duyckaerts, C.; Camonis, J. H.; Brice, A.: Ataxin-7 interacts with
a Cbl-associated protein that it recruits into neuronal intranuclear
inclusions. Hum. Molec. Genet. 10: 1201-1213, 2001.
6. Lesniewski, L. A.; Hosch, S. E.; Neels, J. G.; de Luca, C.; Pashmforoush,
M.; Lumeng, C. N.; Chiang, S.-H.; Scadeng, M.; Saltiel, A. R.; Olefsky,
J. M.: Bone marrow-specific Cap gene deletion protects against high-fat
diet-induced insulin resistance. Nature Med. 13: 455-462, 2007.
7. Liang, X.; Schnetz-Boutaud, N.; Bartlett, J.; Allen, M. J.; Gwirtsman,
H.; Schmechel, D. E.; Carney, R. M.; Gilbert J. R.; Pericak-Vance,
M. A.; Haines, J. L.: No association between SNP rs498055 on chromosome
10 and late-onset Alzheimer disease in multiple datasets. Ann. Hum.
Genet. 72: 141-144, 2008.
8. Lin, W.-H.; Chiu, K. C.; Chang, H.-M.; Lee, K.-C.; Tai, T.-Y.;
Chuang, L.-M.: Molecular scanning of the human sorbin and SH3-domain-containing-1
(SORBS1) gene: positive association of the T228A polymorphism with
obesity and type 2 diabetes. Hum. Molec. Genet. 10: 1753-1760, 2001.
9. Mastick, C. C.; Brady, M. J.; Saltiel, A. R.: Insulin stimulates
the tyrosine phosphorylation of caveolin. J. Cell Biol. 129: 1523-1531,
1995.
10. Ribon, V.; Printen, J. A.; Hoffman, N. G.; Kay, B. K.; Saltiel,
A. R.: A novel, multifunctional c-Cbl binding protein in insulin
receptor signaling in 3T3-L1 adipocytes. Molec. Cell. Biol. 18:
872-879, 1998.
11. Scott, A. F.: Personal Communication. Baltimore, Md. 9/13/2000.
*FIELD* CN
Joanna S. Amberger - updated: 10/6/2008
Marla J. F. O'Neill - updated: 6/5/2007
Victor A. McKusick - updated: 6/13/2006
Victor A. McKusick - updated: 12/29/2005
Joanna S. Amberger - updated: 7/16/2002
George E. Tiller - updated: 2/5/2002
George E. Tiller - updated: 10/19/2001
Ada Hamosh - updated: 4/16/2001
*FIELD* CD
Ada Hamosh: 9/13/2000
*FIELD* ED
ckniffin: 03/16/2011
alopez: 10/23/2008
carol: 10/7/2008
joanna: 10/6/2008
wwang: 6/7/2007
terry: 6/5/2007
wwang: 2/23/2007
mgross: 11/20/2006
terry: 6/13/2006
terry: 2/3/2006
terry: 12/29/2005
alopez: 11/5/2003
joanna: 7/16/2002
cwells: 2/13/2002
cwells: 2/5/2002
cwells: 10/30/2001
cwells: 10/19/2001
alopez: 4/18/2001
terry: 4/16/2001
alopez: 3/28/2001
alopez: 9/13/2000