RBCC

Full text data of SWAP70

SWAP70 (KIAA0640) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Switch-associated protein 70; SWAP-70

hRBCD IPI00307200
IPI00307200 Similar to SWAP-70 Similar to SWAP-70 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a cytoskeleton associated n/a found at its expected molecular weight found at molecular weight

UniProt Q9UH65
ID SWP70_HUMAN Reviewed; 585 AA.
AC Q9UH65; D3DQV1; O75135; Q7LCY6; Q9P061; Q9P0Z8;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Switch-associated protein 70;
DE Short=SWAP-70;
GN Name=SWAP70; Synonyms=KIAA0640; ORFNames=HSPC321;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, PHOSPHORYLATION, AND MUTAGENESIS OF TRP-297.
RX PubMed=10681448; DOI=10.1073/pnas.040374497;
RA Masat L., Caldwell J., Armstrong R., Khoshnevisan H., Jessberger R.,
RA Herndier B., Wabl M., Ferrick D.;
RT "Association of SWAP-70 with the B cell antigen receptor complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2180-2184(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-505.
RX PubMed=11726218; DOI=10.1006/clim.2001.5116;
RA Rapalus L., Minegishi Y., Lavoie A., Cunningham-Rundles C.,
RA Conley M.E.;
RT "Analysis of SWAP-70 as a candidate gene for non-X-linked hyper IgM
RT syndrome and common variable immunodeficiency.";
RL Clin. Immunol. 101:270-275(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-505.
RA Monz D.W., Comtesse N.E., Heckel D.;
RT "Human SWAP-70 homolog.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-505.
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-505.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 355-543.
RC TISSUE=Umbilical cord blood;
RA Ye M., Zhang Q.-H., Zhou J., Shen Y., Wu X.-Y., Guan Z.Q., Wang L.,
RA Fan H.-Y., Mao Y.-F., Dai M., Huang Q.-H., Chen S.-J., Chen Z.;
RT "Human partial CDS from CD34+ stem cells.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 223-ARG-ARG-224; ARG-230 AND 526-MET--GLU-585.
RX PubMed=12925760; DOI=10.1091/mbc.E03-01-0043;
RA Hilpelae P., Oberbanscheidt P., Hahne P., Hund M., Kalhammer G.,
RA Small J.V., Baehler M.;
RT "SWAP-70 identifies a transitional subset of actin filaments in motile
RT cells.";
RL Mol. Biol. Cell 14:3242-3253(2003).
RN [9]
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 [10]
RP STRUCTURE BY NMR OF 211-312.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PH domain of KIAA0640 protein from human.";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: Phosphatidylinositol 3,4,5-trisphosphate-dependent
CC guanine nucleotide exchange factor (GEF) which, independently of
CC RAS, transduces signals from tyrosine kinase receptors to RAC. It
CC also mediates signaling of membrane ruffling. Regulates the actin
CC cytoskeleton as an effector or adapter protein in response to
CC agonist stimulated phosphatidylinositol (3,4)-bisphosphate
CC production and cell protrusion (By similarity).
CC -!- SUBUNIT: The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70
CC (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Nucleus. Cell
CC projection, lamellipodium. Note=In resting B-cells it is localized
CC mainly in the cytoplasm and upon cell activation it is recruited
CC to the plasma membrane and then translocates to the nucleus. In
CC activated, class-switching B-cells it is associated with membrane
CC IgG but not IgM. Localized to loose actin filament arrays located
CC behind actively extending lamellipodia.
CC -!- TISSUE SPECIFICITY: Expressed only in mature B-cells including
CC those associated with mucosa-associated tissue and bronchus-
CC associated tissue (PubMed:10681448). Widely expressed. Abundant in
CC spleen, and fairly abundant in kidney, lung and liver. Also found
CC in monocytes and macrophages (PubMed:12925760).
CC -!- DOMAIN: The PH domain is essential for phosphatidylinositol 3,4,5-
CC trisphosphate binding.
CC -!- PTM: Tyrosine-phosphorylated.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF28999.1; Type=Frameshift; Positions=480, 483;
CC Sequence=BAA31615.1; Type=Erroneous initiation;
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DR EMBL; AF210818; AAF24486.1; -; mRNA.
DR EMBL; AF134894; AAF61403.1; -; mRNA.
DR EMBL; AB014540; BAA31615.1; ALT_INIT; mRNA.
DR EMBL; CH471064; EAW68582.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68583.1; -; Genomic_DNA.
DR EMBL; BC000616; AAH00616.1; -; mRNA.
DR EMBL; AF161439; AAF28999.1; ALT_FRAME; mRNA.
DR PIR; T00379; T00379.
DR RefSeq; NP_055870.2; NM_015055.2.
DR UniGene; Hs.153026; -.
DR PDB; 2DN6; NMR; -; A=211-312.
DR PDBsum; 2DN6; -.
DR ProteinModelPortal; Q9UH65; -.
DR SMR; Q9UH65; 211-315.
DR IntAct; Q9UH65; 2.
DR STRING; 9606.ENSP00000315630; -.
DR PhosphoSite; Q9UH65; -.
DR DMDM; 74753323; -.
DR PaxDb; Q9UH65; -.
DR PeptideAtlas; Q9UH65; -.
DR PRIDE; Q9UH65; -.
DR Ensembl; ENST00000318950; ENSP00000315630; ENSG00000133789.
DR GeneID; 23075; -.
DR KEGG; hsa:23075; -.
DR UCSC; uc001mhv.3; human.
DR CTD; 23075; -.
DR GeneCards; GC11P009642; -.
DR HGNC; HGNC:17070; SWAP70.
DR HPA; HPA006810; -.
DR MIM; 604762; gene.
DR neXtProt; NX_Q9UH65; -.
DR PharmGKB; PA165543694; -.
DR eggNOG; NOG117655; -.
DR HOGENOM; HOG000285974; -.
DR HOVERGEN; HBG053201; -.
DR InParanoid; Q9UH65; -.
DR OMA; SMAINEV; -.
DR OrthoDB; EOG7H1JK5; -.
DR ChiTaRS; SWAP70; human.
DR EvolutionaryTrace; Q9UH65; -.
DR GeneWiki; SWAP70; -.
DR GenomeRNAi; 23075; -.
DR NextBio; 44184; -.
DR PRO; PR:Q9UH65; -.
DR ArrayExpress; Q9UH65; -.
DR Bgee; Q9UH65; -.
DR Genevestigator; Q9UH65; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Coiled coil;
KW Complete proteome; Cytoplasm; DNA-binding; Membrane; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 585 Switch-associated protein 70.
FT /FTId=PRO_0000240280.
FT DOMAIN 210 306 PH.
FT COILED 316 539 Potential.
FT COMPBIAS 291 294 Poly-Lys.
FT VARIANT 230 230 R -> G (in dbSNP:rs397686).
FT /FTId=VAR_059548.
FT VARIANT 505 505 Q -> E (in dbSNP:rs415895).
FT /FTId=VAR_026717.
FT MUTAGEN 223 224 RR->EE: Abolishes binding to
FT phosphatidylinositol 3,4-bisphosphate and
FT phosphatidic acid and the localization to
FT the loose actin filament arrays.
FT MUTAGEN 230 230 R->C: Reduced binding to
FT phosphatidylinositol 3,4-bisphosphate and
FT reduced association with actin filament.
FT MUTAGEN 297 297 W->A: Abolishes binding to plasma
FT membrane.
FT MUTAGEN 526 585 Missing: Affects targeting to loose actin
FT filament arrays.
FT CONFLICT 385 385 A -> S (in Ref. 7).
FT STRAND 212 220
FT STRAND 227 234
FT STRAND 239 244
FT STRAND 248 254
FT STRAND 261 265
FT STRAND 273 278
FT STRAND 283 287
FT HELIX 291 310
SQ SEQUENCE 585 AA; 68998 MW; B42B63CF033E612F CRC64;
MGSLKEELLK AIWHAFTALD QDHSGKVSKS QLKVLSHNLC TVLKVPHDPV ALEEHFRDDD
EGPVSNQGYM PYLNRFILEK VQDNFDKIEF NRMCWTLCVK KNLTKNPLLI TEEDAFKIWV
IFNFLSEDKY PLIIVSEEIE YLLKKLTEAM GGGWQQEQFE HYKINFDDSK NGLSAWELIE
LIGNGQFSKG MDRQTVSMAI NEVFNELILD VLKQGYMMKK GHRRKNWTER WFVLKPNIIS
YYVSEDLKDK KGDILLDENC CVESLPDKDG KKCLFLVKCF DKTFEISASD KKKKQEWIQA
IHSTIHLLKL GSPPPHKEAR QRRKELRKKQ LAEQEELERQ MKELQAANES KQQELEAVRK
KLEEAASRAA EEEKKRLQTQ VELQARFSTE LEREKLIRQQ MEEQVAQKSS ELEQYLQRVR
ELEDMYLKLQ EALEDERQAR QDEETVRKLQ ARLLEEESSK RAELEKWHLE QQQAIQTTEA
EKQELENQRV LKEQALQEAM EQLEQLELER KQALEQYEEV KKKLEMATNK TKSWKDKVAH
HEGLIRLIEP GSKNPHLITN WGPAAFTEAE LEEREKNWKE KKTTE
//

MIM 604762
*RECORD*
*FIELD* NO
604762
*FIELD* TI
*604762 SWITCH-ASSOCIATED PROTEIN 70
;;SWAP70
*FIELD* TX

CLONING

The B-cell receptor is composed of the immunoglobulin (Ig) heavy and
read morelight chains and the covalently bound accessory molecules Ig-alpha
(CD79A; 112205) and Ig-beta (CD79B; 147245). Crosslinking of the B-cell
receptor by antigens stimulates the activation of intracellular protein
kinases. B-cell activation leads to hypermutation of the Ig variable
regions and to heavy chain class switching, in which the Ig constant
region of mu (IgM; see 147020) is replaced by that of another class:
gamma (IgG; see 147100), alpha (IgA; see 146900), or epsilon (IgE; see
147180). Class switching is achieved by a looping out and deletion
mechanism between the switch region of mu and the switch region of the
isotope that is to be expressed. Masat et al. (2000) explored the
possibility that switch-associated protein-70 (SWAP70) acts as a link
between the recognition of specific switch regions and causation of a
DNA break. Swap70 had been isolated in the mouse as part of a complex
that is able to promote recombination between 2 switch regions in vitro
(Borggrefe et al., 1998; Borggrefe et al., 1999). By screening a human
lymphoma cDNA library using mouse Swap70 sequences as the probe, Masat
et al. (2000) isolated a cDNA encoding SWAP70. Although the 585-amino
acid SWAP70 protein contains 3 nuclear localization signals, SWAP70 was
found mainly in the cytoplasm in small resting B cells. On stimulation,
SWAP70 translocated to the nucleus. In activated, class-switching B cell
cultures, it was associated with membrane IgG, but not IgM. Masat et al.
(2000) suggested that SWAP70 is involved not only in nuclear events but
also in signaling in B-cell activation.

GENE FUNCTION

Shinohara et al. (2002) demonstrated that SWAP70 specifically binds
phosphatidylinositol-3,4,5-triphosphate. On stimulation by growth
factors, cytoplasmic SWAP70, which is dependent on
phosphoinositide-3-hydroxykinase but independent of Ras (see 190020),
moved to cell membrane rearrangements known as ruffles. However, mutant
SWAP70 lacking the ability to bind
phosphatidylinositol-3,4,5-triphosphate blocked membrane ruffling
induced by epidermal growth factor (EGF; 131530) or platelet-derived
growth factor (see 173430). SWAP70 shows low homology with Rac-guanine
nucleotide exchange factors, and catalyzes
phosphatidylinositol-3,4,5-triphosphate-dependent guanine nucleotide
exchange to Rac (see 602048). SWAP70-deficient fibroblasts showed
impaired membrane ruffling after stimulation with EGF, and failed to
activate Rac fully. Shinohara et al. (2002) concluded that SWAP70 is a
different type of Rac-GEF which, independently of Ras, transduces
signals from tyrosine kinase receptors to Rac.

MAPPING

By FISH, Masat et al. (2000) mapped the human SWAP70 gene to 11p15 in a
region that shows homology of synteny to mouse chromosome 7. They used
linkage analysis and FISH on metaphase chromosomes to map the mouse
Swap70 gene to mid-chromosome 7.

ANIMAL MODEL

B cells migrate directly from the blood stream to secondary lymphoid
organs and lymph nodes. Before diapedesis, these cells roll in an
L-selectin (SELE; 153240)-dependent manner, receive signals through CCR7
(600242) and CXCR4 (162643), and adhere to high endothelial venules
(HEVs) via integrin alpha-L (ITGAL; 153370)/beta-2 (ITGB2; 600065).
Pearce et al. (2006) observed reduced lymph node swelling in Swap70 -/-
mice, with reduced accumulation of B cells, particularly of the B2
subset, following footpad immunization. In vitro assays showed that
Swap70 -/- B cells expressed chemokine receptors and responded to
chemokines. Immunohistochemical analysis demonstrated that Swap70 -/- B
cells accumulated in HEVs due to aberrant regulation of
integrin-mediated adhesion. Pearce et al. (2006) concluded that SWAP70
regulates processes essential for B-cell entry into lymph nodes.

*FIELD* RF
1. Borggrefe, T.; Masat, L.; Wabl, M.; Riwar, B.; Cattoretti, G.;
Jessberger, R.: Cellular, intracellular, and developmental expression
patterns of murine SWAP-70. Europ. J. Immun. 29: 1812-1822, 1999.

2. Borggrefe, T.; Wabl, M.; Akhmedov, A. T.; Jessberger, R.: A B-cell-specific
DNA recombination complex. J. Biol. Chem. 273: 17025-17035, 1998.

3. Masat, L.; Caldwell, J.; Armstrong, R.; Khoshnevisan, H.; Jessberger,
R.; Herndier, B.; Wabl, M.; Ferrick, D.: Association of SWAP-70 with
the B cell antigen receptor complex. Proc. Nat. Acad. Sci. 97: 2180-2184,
2000.

4. Masat, L.; Liddell, R. A.; Mock, B. A.; Kuo, W.-L.; Jessberger,
R.; Wabl, M.; Morse, H. C., III: Mapping of the SWAP70 gene to mouse
chromosome 7 and human chromosome 11p15. Immunogenetics 51: 16-19,
2000.

5. Pearce, G.; Angeli, V.; Randolph, G. J.; Junt, T.; von Andrian,
U.; Schnittler, H.-J.; Jessberger, R.: Signaling protein SWAP-70
is required for efficient B cell homing to lymphoid organs. Nature
Immun. 7: 827-834, 2006.

6. Shinohara, M.; Terada, Y.; Iwamatsu, A.; Shinohara, A.; Mochizuki,
N.; Higuchi, M.; Gotoh, Y.; Ihara, S.; Nagata, S.; Itoh, H.; Fukui,
Y.; Jessberger, R.: SWAP-70 is a guanine-nucleotide-exchange factor
that mediates signalling of membrane ruffling. Nature 416: 759-763,
2002.

*FIELD* CN
Paul J. Converse - updated: 12/12/2006
Ada Hamosh - updated: 4/30/2002
Victor A. McKusick - updated: 4/11/2000

*FIELD* CD
Victor A. McKusick: 3/30/2000

*FIELD* ED
mgross: 12/20/2006
terry: 12/12/2006
alopez: 4/30/2002
terry: 4/30/2002
mcapotos: 5/2/2000
mcapotos: 4/27/2000
terry: 4/11/2000
mgross: 3/30/2000

RBCC Red Blood Cell Collection

Full text data of SWAP70