TIAM1_MOUSE
ID TIAM1_MOUSE Reviewed; 1591 AA.
AC Q60610;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Rho guanine nucleotide exchange factor TIAM1 {ECO:0000305};
DE AltName: Full=T-lymphoma invasion and metastasis-inducing protein 1 {ECO:0000305|PubMed:7999144};
DE Short=TIAM-1 {ECO:0000303|PubMed:7999144};
GN Name=Tiam1 {ECO:0000312|MGI:MGI:103306};
GN Synonyms=Tiam-1 {ECO:0000303|PubMed:7999144};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=7999144; DOI=10.1016/0092-8674(94)90216-x;
RA Habets G.G.M., Scholtes E.H.M., Zuydgeest D., van der Kammen R.A.,
RA Stam J.C., Berns A., Collard J.G.;
RT "Identification of an invasion-inducing gene, Tiam-1, that encodes a
RT protein with homology to GDP-GTP exchangers for Rho-like proteins.";
RL Cell 77:537-549(1994).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [4]
RP INTERACTION WITH NTRK2, AND PHOSPHORYLATION AT TYR-829 BY NTRK2.
RX PubMed=16801538; DOI=10.1073/pnas.0603914103;
RA Miyamoto Y., Yamauchi J., Tanoue A., Wu C., Mobley W.C.;
RT "TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of
RT Rac1 and induction of changes in cellular morphology.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10444-10449(2006).
RN [5]
RP SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF 459-ARG-ARG-460, AND
RP LIPID-BINDING.
RX PubMed=17339315; DOI=10.1074/jbc.m700505200;
RA Ceccarelli D.F., Blasutig I.M., Goudreault M., Li Z., Ruston J., Pawson T.,
RA Sicheri F.;
RT "Non-canonical interaction of phosphoinositides with pleckstrin homology
RT domains of Tiam1 and ArhGAP9.";
RL J. Biol. Chem. 282:13864-13874(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1323, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; SER-356; SER-358;
RP SER-695 AND SER-1519, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP INTERACTION WITH EPHA8.
RX PubMed=20496116; DOI=10.1007/s10059-010-0075-2;
RA Yoo S., Shin J., Park S.;
RT "EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is regulated by
RT Tiam-1, a Rac-specific guanine nucleotide exchange factor.";
RL Mol. Cells 29:603-609(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1033-1406 IN COMPLEX WITH RAC1.
RX PubMed=11130063; DOI=10.1038/35047014;
RA Worthylake D.K., Rossman K.L., Sondek J.;
RT "Crystal structure of Rac1 in complex with the guanine nucleotide exchange
RT region of Tiam1.";
RL Nature 408:682-688(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (4.5 ANGSTROMS) OF 429-702, AND INTERACTION WITH
RP CD44; PARD3 AND MAPK8IP2.
RX PubMed=19893486; DOI=10.1038/emboj.2009.323;
RA Terawaki S., Kitano K., Mori T., Zhai Y., Higuchi Y., Itoh N., Watanabe T.,
RA Kaibuchi K., Hakoshima T.;
RT "The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding
RT module.";
RL EMBO J. 29:236-250(2010).
CC -!- FUNCTION: Guanyl-nucleotide exchange factor that activates RHO-like
CC proteins and connects extracellular signals to cytoskeletal activities.
CC Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream
CC signaling to regulate processes like cell adhesion and cell migration.
CC {ECO:0000250|UniProtKB:Q13009}.
CC -!- SUBUNIT: Component of the Par polarity complex, composed of at least
CC phosphorylated PRKCZ, PARD3 and TIAM1 (By similarity). Interacts with
CC BAIAP2. Interacts (via PDZ domain) with CNTNAP4, SDC1 and SDC3 (via C-
CC terminus) (By similarity). Interacts with CD44, PARD3 and MAPK8IP2.
CC Interacts with EPHA8; regulates clathrin-mediated endocytosis of EPHA8.
CC Interacts with NTRK2; mediates the activation of RAC1 by BDNF.
CC {ECO:0000250, ECO:0000269|PubMed:11130063, ECO:0000269|PubMed:16801538,
CC ECO:0000269|PubMed:19893486, ECO:0000269|PubMed:20496116}.
CC -!- INTERACTION:
CC Q60610; P15379: Cd44; NbExp=8; IntAct=EBI-1030321, EBI-7565891;
CC -!- SUBCELLULAR LOCATION: Cell junction {ECO:0000269|PubMed:17339315}. Cell
CC membrane {ECO:0000269|PubMed:17339315}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17339315}; Cytoplasmic side
CC {ECO:0000269|PubMed:17339315}. Note=Presence of KRIT1, CDH5 and RAP1B
CC is required for its localization to the cell junction (By similarity).
CC Detected at the boundary between cells with actin-rich protrusions.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and testis and at low or
CC moderate levels in almost all other normal tissues. Found in virtually
CC all analyzed tumor cell lines including B- and T-lymphomas,
CC neuroblastomas, melanomas and carcinomas.
CC -!- DOMAIN: The first PH domain mediates interaction with membranes
CC enriched in phosphoinositides. {ECO:0000269|PubMed:17339315}.
CC -!- PTM: Ubiquitinated. Undergoes 'Lys-48' ubiquitination at Lys-1404 and
CC Lys-1420 by a CUL3(KBTBD6/7) E3 ubiquitin ligase complex composed of
CC CUL3, RBX1, KBTBD6 and KBTBD7. 'Lys-48' ubiquitination at Lys-1404 and
CC Lys-1420 triggers proteasomal degradation. Ubiquitination at Lys-1404
CC and Lys-1420 by CUL3(KBTBD6/7) also requires the membrane-associated
CC protein GABARAP and may therefore be spatially restricted within the
CC cell. {ECO:0000250|UniProtKB:Q13009}.
CC -!- SIMILARITY: Belongs to the TIAM family. {ECO:0000305}.
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DR EMBL; U05245; AAA18830.1; -; mRNA.
DR CCDS; CCDS28314.1; -.
DR PIR; A54146; A54146.
DR PDB; 1FOE; X-ray; 2.80 A; A/C/E/G=1033-1406.
DR PDB; 3A8N; X-ray; 4.50 A; A=429-702.
DR PDB; 7UIQ; X-ray; 3.11 A; C/D=1541-1559.
DR PDB; 7UIR; X-ray; 3.10 A; C/D=1541-1559.
DR PDBsum; 1FOE; -.
DR PDBsum; 3A8N; -.
DR PDBsum; 7UIQ; -.
DR PDBsum; 7UIR; -.
DR AlphaFoldDB; Q60610; -.
DR SMR; Q60610; -.
DR CORUM; Q60610; -.
DR DIP; DIP-37821N; -.
DR IntAct; Q60610; 8.
DR MINT; Q60610; -.
DR STRING; 10090.ENSMUSP00000126020; -.
DR iPTMnet; Q60610; -.
DR PhosphoSitePlus; Q60610; -.
DR SWISS-2DPAGE; Q60610; -.
DR EPD; Q60610; -.
DR jPOST; Q60610; -.
DR MaxQB; Q60610; -.
DR PaxDb; Q60610; -.
DR PRIDE; Q60610; -.
DR ProteomicsDB; 262778; -.
DR ABCD; Q60610; 1 sequenced antibody.
DR MGI; MGI:103306; Tiam1.
DR eggNOG; KOG3519; Eukaryota.
DR InParanoid; Q60610; -.
DR PhylomeDB; Q60610; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR ChiTaRS; Tiam1; mouse.
DR EvolutionaryTrace; Q60610; -.
DR PRO; PR:Q60610; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60610; protein.
DR GO; GO:0044291; C:cell-cell contact zone; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0060091; C:kinocilium; IDA:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0000242; C:pericentriolar material; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; IDA:MGI.
DR GO; GO:0005543; F:phospholipid binding; IDA:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:MGI.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IMP:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0016601; P:Rac protein signal transduction; ISS:UniProtKB.
DR GO; GO:1904338; P:regulation of dopaminergic neuron differentiation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:2000050; P:regulation of non-canonical Wnt signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:MGI.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR003116; RBD_dom.
DR InterPro; IPR033360; Tiam1.
DR InterPro; IPR043537; Tiam1/Tiam2/Sif.
DR InterPro; IPR040655; TIAM1_CC-Ex.
DR PANTHER; PTHR46001; PTHR46001; 1.
DR PANTHER; PTHR46001:SF1; PTHR46001:SF1; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF00169; PH; 2.
DR Pfam; PF02196; RBD; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF18385; Tiam_CC_Ex; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50898; RBD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cell membrane;
KW Guanine-nucleotide releasing factor; Isopeptide bond; Lipid-binding;
KW Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..1591
FT /note="Rho guanine nucleotide exchange factor TIAM1"
FT /id="PRO_0000080977"
FT DOMAIN 434..549
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 765..832
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 845..908
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1040..1234
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1261..1397
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 393..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 933..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1456..1481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..45
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..380
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 958..975
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1011..1034
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 829
FT /note="Phosphotyrosine; by NTRK2"
FT /evidence="ECO:0000269|PubMed:16801538"
FT MOD_RES 1323
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 1519
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT CROSSLNK 1404
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13009"
FT CROSSLNK 1420
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13009"
FT MUTAGEN 459..460
FT /note="RR->AA: Reduces phosphatidylinositol phosphate
FT binding."
FT /evidence="ECO:0000269|PubMed:17339315"
FT MUTAGEN 622
FT /note="R->A: Reduces PARD3 binding; when associated with A-
FT 645."
FT MUTAGEN 645
FT /note="R->A: Reduces PARD3 binding; when associated with A-
FT 622."
FT HELIX 1037..1065
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1067..1071
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1073..1076
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1078..1085
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1088..1106
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1112..1114
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1118..1121
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1122..1135
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1138..1141
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1142..1148
FT /evidence="ECO:0007829|PDB:1FOE"
FT TURN 1149..1151
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1152..1156
FT /evidence="ECO:0007829|PDB:1FOE"
FT TURN 1157..1161
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1163..1172
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1178..1180
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1182..1185
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1188..1193
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1196..1205
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1212..1249
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1264..1266
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1267..1277
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1280..1283
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1290..1296
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1299..1304
FT /evidence="ECO:0007829|PDB:1FOE"
FT TURN 1318..1321
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1332..1336
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1337..1339
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1340..1343
FT /evidence="ECO:0007829|PDB:1FOE"
FT TURN 1348..1351
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1355..1360
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1365..1367
FT /evidence="ECO:0007829|PDB:1FOE"
FT STRAND 1371..1379
FT /evidence="ECO:0007829|PDB:1FOE"
FT HELIX 1380..1400
FT /evidence="ECO:0007829|PDB:1FOE"
SQ SEQUENCE 1591 AA; 177533 MW; ECC2BAB189A6F019 CRC64;
MGNAESQNVD HEFYGEKHAS LGRKHTSRSL RLSHKTRRTR HASSGKAIHR NSEVSTRSSS
TPSIPQSLAE NGLEPFSQEG ALDDFGDPIW VDRVDMGLRP VSYTDSSVTP SVDGSIVLTA
ASVQSMPDSE ESRLYGDDAT YLAEGGRRQC PYTSNGPTFM ETASFKKKRS KSADIWREDS
LEFSLSDLSQ EHLTSNEEIL GSAEEKDCEE ARGMETEASP RQLSTCQRAN SLGDLYAQKN
SGVKANGGPR NRFSSYCRNL VSDIPDLAKH KMPPAAAEET PPYSNYNTLP CRKSHCLSEG
ATNPQISLSK SMQGRRAKTT QDVNTGEGSE FADSGIEGAT TDTDLLSRRS NATNSSYSPP
TGRAFVGSDS GSSSTGDRAR QGVYENFRRE LEMSTTNSES LEEAGSAHSD EQSSGTLSSP
GQSDILLTAA QGTVRKAGAL AVKNFLVHKK NKKVESATRR KWKHYWVSLK GCTLFFYETD
GRSGIDHNSV PKHAVWVENS IVQAVPEHPK KDFVFCLSNS LGDAFLFQTT SQTELENWIT
AIHSACAAAV ARHHHKEDTL RLLKSEIKKL EQKIDMDEKM KKMGEMQLSS VTDSKKKKTI
LDQIFVWEQN LEQFQMDLFR FRCYLASLQG GELPNPKRLL AFASRPTKVA MGRLGIFSVS
SFHALVAART GEIGVRRRTQ AMSRSASKRR SRFSSLWGLD TTSKKKQGRP TINQVFGEGT
DAVKRSLEGI FDDTVPDGKR EKEVVLPSVH QHNPDCDIWV HEYFTPSWFC LPNNQPALTV
VRPGDTARDT LELICKTHQL DHSAHYLRLK FLMENRVQFY IPQPEEDIYE LLYKEIEICP
KVTQNIHIEK SDAAADNYGF LLSSVDEDGI RRLYVNSVKE TGLASKKGLK AGDEILEINN
RAAGTLNSSM LKDFLSQPSL GLLVRTYPEP EGGVELLENP PHRVDGPVDL GESPLAFLTS
NPGHSLSSEQ GSSAETAPEE GEGPDLESSD ETDHSSKSTE QVAAFCRSLH EMSPSDSSPS
PQDATSPQLA TTRQLSDADK LRKVICELLE TERTYVKDLN CLMERYLKPL QKETFLTQDE
LDVLFGNLTE MVEFQVEFLK TLEDGVRLVP DLEKLEKVDQ FKKVLFSLGG SFLYYADRFK
LYSAFCASHT KVPKVLVKAK TDTAFKAFLD AQNPRQQHSS TLESYLIKPI QRVLKYPLLL
RELFALTDAE SEEHYHLDVA IKTMNKVASH INEMQKIHEE FGAVFDQLIA EQTGEKKEVA
DLSMGDLLLH TSVIWLNPPA SLGKWKKEPE LAAFVFKTAV VLVYKDGSKQ KKKLVGSHRL
SIYEEWDPFR FRHMIPTEAL QVRALPSADA EANAVCEIVH VKSESEGRPE RVFHLCCSSP
ESRKDFLKSV HSILRDKHRR QLLKTESLPS AQQYVPFGGK RLCALKGARP AMSRAVSAPS
KSLGRRRRRL ARNRFTIDSD AISASSPEKE PQQPAGGGDT DRWVEEQFDL AQYEEQDDIK
ETDILSDDDE FCESLKGASV DRDLQEQLQA ASISQRARGR RTLDSHASRM TQLKKQAALS
GINGGLESAS EEVIWVRRED FAPSRKLNTE I
