Full text data of CYFIP1
CYFIP1
(KIAA0068)
[Confidence: low (only semi-automatic identification from reviews)]
Cytoplasmic FMR1-interacting protein 1 (Specifically Rac1-associated protein 1; Sra-1; p140sra-1)
Cytoplasmic FMR1-interacting protein 1 (Specifically Rac1-associated protein 1; Sra-1; p140sra-1)
UniProt
Q7L576
ID CYFP1_HUMAN Reviewed; 1253 AA.
AC Q7L576; A8K6D9; Q14467; Q5IED0; Q6ZSX1; Q9BSD9; Q9BVC7;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 86.
DE RecName: Full=Cytoplasmic FMR1-interacting protein 1;
DE AltName: Full=Specifically Rac1-associated protein 1;
DE Short=Sra-1;
DE AltName: Full=p140sra-1;
GN Name=CYFIP1; Synonyms=KIAA0068;
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 AND 3), AND VARIANT SER-820.
RA Jiang Y.-H., Beaudet A.L.;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S.,
RA Seki N., Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II.
RT The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP SER-820.
RC TISSUE=Brain, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 50-58; 111-130; 151-163; 366-377; 441-448;
RP 505-515; 564-573; 754-760; 815-826; 867-877; 1054-1076; 1211-1224 AND
RP 1228-1240, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, and Hepatoma;
RA Bienvenut W.V., Claeys D., Boldt K., von Kriegsheim A.F., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [7]
RP FUNCTION.
RX PubMed=9417078; DOI=10.1074/jbc.273.1.291;
RA Kobayashi K., Kuroda S., Fukata M., Nakamura T., Nagase T., Nomura N.,
RA Matsuura Y., Yoshida-Kubomura N., Iwamatsu A., Kaibuchi K.;
RT "p140Sra-1 (specifically Rac1-associated protein) is a novel specific
RT target for Rac1 small GTPase.";
RL J. Biol. Chem. 273:291-295(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH DPYSL2.
RX PubMed=16260607; DOI=10.1128/MCB.25.22.9920-9935.2005;
RA Kawano Y., Yoshimura T., Tsuboi D., Kawabata S., Kaneko-Kawano T.,
RA Shirataki H., Takenawa T., Kaibuchi K.;
RT "CRMP-2 is involved in kinesin-1-dependent transport of the Sra-
RT 1/WAVE1 complex and axon formation.";
RL Mol. Cell. Biol. 25:9920-9935(2005).
RN [9]
RP FUNCTION.
RX PubMed=19524508; DOI=10.1016/j.cell.2009.04.013;
RA Silva J.M., Ezhkova E., Silva J., Heart S., Castillo M., Campos Y.,
RA Castro V., Bonilla F., Cordon-Cardo C., Muthuswamy S.K., Powers S.,
RA Fuchs E., Hannon G.J.;
RT "Cyfip1 is a putative invasion suppressor in epithelial cancers.";
RL Cell 137:1047-1061(2009).
RN [10]
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF WAVE1 COMPLEX, FUNCTION,
RP INTERACTION WITH RAC1, MUTAGENESIS OF CYS-179; ARG-190; GLU-434;
RP PHE-626; MET-632; LEU-697; TYR-704; LEU-841 AND 844-PHE-TRP-845, AND
RP SUBUNIT.
RX PubMed=21107423; DOI=10.1038/nature09623;
RA Chen Z., Borek D., Padrick S.B., Gomez T.S., Metlagel Z., Ismail A.M.,
RA Umetani J., Billadeau D.D., Otwinowski Z., Rosen M.K.;
RT "Structure and control of the actin regulatory WAVE complex.";
RL Nature 468:533-538(2010).
CC -!- FUNCTION: Component of the CYFIP1-EIF4E-FMR1 complex which binds
CC to the mRNA cap and mediates translational repression. In the
CC CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E
CC and FMR1. Promotes the translation repression activity of FMR1 in
CC brain probably by mediating its association with EIF4E and mRNA
CC (By similarity). Regulates formation of membrane ruffles and
CC lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but
CC not to RNA. Part of the WAVE complex that regulates actin filament
CC reorganization via its interaction with the Arp2/3 complex. Actin
CC remodeling activity is regulated by RAC1. Regulator of epithelial
CC morphogenesis. May act as an invasion suppressor in cancers.
CC -!- SUBUNIT: Component of the WAVE1 complex composed of ABI2, CYFIP1
CC or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a
CC heterdimer containing NCKAP1 and CYFIP1 interacts with a
CC heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the
CC CYFIP1-EIF4E-FMR1 complex which is composed of CYFIP, EIF4E and
CC FMR1. Interacts with FMR1 but does not bind to related proteins
CC FXR1 or FXR2. Interaction with EIF4E stimulates FMR1 binding.
CC Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1,
CC NCKAP1/NAP1 and WASF2/WAVE2. Interacts with the active GTP-bound
CC form of RAC1. Interacts through its C-terminus with the C-terminus
CC of DPYSL2/CRMP2 which is necessary for DPYSL2-induced axon
CC outgrowth. Interacts with NYAP1, NYAP2 and MYO16.
CC -!- INTERACTION:
CC P63073:Eif4e (xeno); NbExp=2; IntAct=EBI-1048143, EBI-2000006;
CC Q06787:FMR1; NbExp=4; IntAct=EBI-1048143, EBI-366305;
CC Q9Y2A7:NCKAP1; NbExp=3; IntAct=EBI-1048143, EBI-389845;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region (By
CC similarity). Cell projection, lamellipodium (By similarity). Cell
CC projection, ruffle (By similarity). Cell junction, synapse,
CC synaptosome (By similarity). Note=Highly expressed in the
CC perinuclear region. Enriched in synaptosomes, membrane ruffles and
CC at the tips of lamellipodia (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=3;
CC IsoId=Q7L576-1; Sequence=Displayed;
CC Name=2; Synonyms=4;
CC IsoId=Q7L576-2; Sequence=VSP_052346, VSP_052347;
CC Name=3; Synonyms=5;
CC IsoId=Q7L576-3; Sequence=VSP_052345;
CC -!- MISCELLANEOUS: Breakpoint hotspot for the Prader-Willi/Angelman
CC syndromes and may be implicated in autism. Commonly altered in
CC tumors.
CC -!- SIMILARITY: Belongs to the CYFIP family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07552.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AY763577; AAW51476.1; -; mRNA.
DR EMBL; AY763578; AAW51477.1; -; mRNA.
DR EMBL; AY763579; AAW51478.1; -; mRNA.
DR EMBL; AY763580; AAW51479.1; -; mRNA.
DR EMBL; D38549; BAA07552.1; ALT_INIT; mRNA.
DR EMBL; AK127094; BAC86825.1; -; mRNA.
DR EMBL; AK291604; BAF84293.1; -; mRNA.
DR EMBL; CH471258; EAW65555.1; -; Genomic_DNA.
DR EMBL; BC001306; AAH01306.2; -; mRNA.
DR EMBL; BC005097; AAH05097.1; -; mRNA.
DR RefSeq; NP_001028200.1; NM_001033028.1.
DR RefSeq; NP_055423.1; NM_014608.2.
DR RefSeq; XP_005272600.1; XM_005272543.1.
DR RefSeq; XP_005272601.1; XM_005272544.1.
DR UniGene; Hs.26704; -.
DR PDB; 3P8C; X-ray; 2.29 A; A=1-1253.
DR PDBsum; 3P8C; -.
DR ProteinModelPortal; Q7L576; -.
DR DIP; DIP-38873N; -.
DR IntAct; Q7L576; 20.
DR MINT; MINT-1731056; -.
DR STRING; 9606.ENSP00000324549; -.
DR PhosphoSite; Q7L576; -.
DR DMDM; 74738589; -.
DR PaxDb; Q7L576; -.
DR PRIDE; Q7L576; -.
DR DNASU; 23191; -.
DR Ensembl; ENST00000313077; ENSP00000324549; ENSG00000068793.
DR Ensembl; ENST00000435939; ENSP00000405956; ENSG00000068793.
DR Ensembl; ENST00000560848; ENSP00000454199; ENSG00000068793.
DR GeneID; 23191; -.
DR KEGG; hsa:23191; -.
DR UCSC; uc001yus.3; human.
DR CTD; 23191; -.
DR GeneCards; GC15P023873; -.
DR HGNC; HGNC:13759; CYFIP1.
DR MIM; 606322; gene.
DR neXtProt; NX_Q7L576; -.
DR Orphanet; 72; Angelman syndrome.
DR PharmGKB; PA38367; -.
DR eggNOG; NOG306641; -.
DR HOGENOM; HOG000272573; -.
DR HOVERGEN; HBG053209; -.
DR InParanoid; Q7L576; -.
DR KO; K05749; -.
DR OMA; SSNIYKL; -.
DR OrthoDB; EOG7ZSHS2; -.
DR PhylomeDB; Q7L576; -.
DR ChiTaRS; CYFIP1; human.
DR EvolutionaryTrace; Q7L576; -.
DR GeneWiki; CYFIP1; -.
DR GenomeRNAi; 23191; -.
DR NextBio; 44673; -.
DR PRO; PR:Q7L576; -.
DR ArrayExpress; Q7L576; -.
DR Bgee; Q7L576; -.
DR CleanEx; HS_CYFIP1; -.
DR Genevestigator; Q7L576; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0048365; F:Rac GTPase binding; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0031529; P:ruffle organization; ISS:UniProtKB.
DR InterPro; IPR008081; Cytoplasmic_FMR1-int.
DR InterPro; IPR016536; Cytoplasmic_FMR1-int_sub.
DR PANTHER; PTHR12195; PTHR12195; 1.
DR Pfam; PF05994; FragX_IP; 1.
DR PIRSF; PIRSF008153; FMR1_interacting; 1.
DR PRINTS; PR01698; CYTOFMRPINTP.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cell junction;
KW Cell projection; Cell shape; Complete proteome; Cytoplasm;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Neurogenesis; Polymorphism; Reference proteome; Synapse; Synaptosome.
FT CHAIN 1 1253 Cytoplasmic FMR1-interacting protein 1.
FT /FTId=PRO_0000279706.
FT VAR_SEQ 1 806 Missing (in isoform 3).
FT /FTId=VSP_052345.
FT VAR_SEQ 1 431 Missing (in isoform 2).
FT /FTId=VSP_052346.
FT VAR_SEQ 432 557 AEEYERATRYNYTSEEKFALVEVIAMIKGLQVLMGRMESVF
FT NHAIRHTVYAALQDFSQVTLREPLRQAIKKKKNVIQSVLQA
FT IRKTVCDWETGHEPFNDPALRGEKDPKSGFDIKVPRRAVGP
FT SST -> MAESLGSAELLRQLKSLGMERLLHAVNTFLRQSC
FT TYLPLLTFGGKTSFVSLDVYGTEANCSATSCSFPKAAATWP
FT RRQAPGPLGELVRGPPDQGVAEQSFSHGLFEFGITNVPCIF
FT SPPQMFPWII (in isoform 2).
FT /FTId=VSP_052347.
FT VARIANT 532 532 A -> P (in dbSNP:rs34683919).
FT /FTId=VAR_053849.
FT VARIANT 820 820 G -> D (in dbSNP:rs17137190).
FT /FTId=VAR_053850.
FT VARIANT 820 820 G -> S (in dbSNP:rs7170637).
FT /FTId=VAR_053851.
FT MUTAGEN 179 179 C->R: Reduced interaction with RAC1.
FT MUTAGEN 190 190 R->D: Reduced interaction with RAC1.
FT MUTAGEN 434 434 E->K: Reduced interaction with RAC1; when
FT associated with A-626.
FT MUTAGEN 626 626 F->A: Reduced interaction with RAC1; when
FT associated with K-434.
FT MUTAGEN 632 632 M->D: Reduced interaction with RAC1.
FT MUTAGEN 697 697 L->D: Constitutive induction of the
FT formation of actin filaments; when
FT associated with D-704.
FT MUTAGEN 704 704 Y->D: Constitutive induction of the
FT formation of actin filaments; when
FT associated with D-697.
FT MUTAGEN 841 841 L->A: Constitutive induction of the
FT formation of actin filaments; when
FT associated with 844-A-A-845.
FT MUTAGEN 844 845 FW->AA: Constitutive induction of the
FT formation of actin filaments; when
FT associated with A-841.
FT CONFLICT 583 583 S -> N (in Ref. 1; AAW51478 and 3;
FT BAC86825).
FT CONFLICT 898 898 Y -> H (in Ref. 1; AAW51478 and 3;
FT BAC86825).
FT CONFLICT 930 930 M -> R (in Ref. 1; AAW51478 and 3;
FT BAC86825).
FT CONFLICT 1176 1176 V -> A (in Ref. 1; AAW51479).
FT HELIX 7 17
FT HELIX 59 84
FT HELIX 90 92
FT HELIX 104 143
FT HELIX 148 150
FT HELIX 155 177
FT HELIX 179 193
FT TURN 194 196
FT HELIX 201 215
FT HELIX 219 229
FT HELIX 234 250
FT HELIX 257 274
FT STRAND 275 278
FT HELIX 281 286
FT HELIX 292 301
FT STRAND 304 308
FT STRAND 311 314
FT HELIX 316 320
FT TURN 323 325
FT HELIX 326 331
FT HELIX 346 365
FT HELIX 384 417
FT TURN 422 424
FT HELIX 434 438
FT HELIX 440 442
FT HELIX 445 467
FT HELIX 469 489
FT TURN 490 492
FT HELIX 493 501
FT HELIX 505 518
FT STRAND 522 525
FT HELIX 531 534
FT HELIX 556 570
FT TURN 580 583
FT HELIX 586 598
FT HELIX 599 601
FT HELIX 602 606
FT HELIX 608 615
FT HELIX 619 621
FT HELIX 625 630
FT TURN 631 633
FT HELIX 640 642
FT HELIX 644 655
FT HELIX 658 660
FT TURN 661 663
FT HELIX 664 668
FT HELIX 670 680
FT HELIX 685 721
FT HELIX 725 733
FT HELIX 747 750
FT STRAND 755 757
FT STRAND 760 762
FT HELIX 764 788
FT HELIX 792 794
FT HELIX 795 813
FT HELIX 821 828
FT STRAND 832 836
FT HELIX 838 849
FT HELIX 851 854
FT STRAND 855 858
FT TURN 859 862
FT STRAND 863 866
FT HELIX 869 871
FT HELIX 885 887
FT HELIX 892 901
FT HELIX 902 906
FT HELIX 911 942
FT HELIX 944 955
FT HELIX 965 967
FT HELIX 969 979
FT HELIX 981 984
FT TURN 987 992
FT HELIX 993 1025
FT HELIX 1026 1029
FT HELIX 1043 1053
FT HELIX 1055 1057
FT HELIX 1059 1066
FT HELIX 1069 1083
FT HELIX 1086 1088
FT STRAND 1090 1092
FT HELIX 1093 1101
FT TURN 1107 1110
FT STRAND 1121 1123
FT HELIX 1127 1139
FT HELIX 1149 1153
FT HELIX 1156 1167
FT HELIX 1171 1177
FT HELIX 1179 1190
FT HELIX 1201 1225
SQ SEQUENCE 1253 AA; 145182 MW; D8F45E13207BEF16 CRC64;
MAAQVTLEDA LSNVDLLEEL PLPDQQPCIE PPPSSLLYQP NFNTNFEDRN AFVTGIARYI
EQATVHSSMN EMLEEGQEYA VMLYTWRSCS RAIPQVKCNE QPNRVEIYEK TVEVLEPEVT
KLMNFMYFQR NAIERFCGEV RRLCHAERRK DFVSEAYLIT LGKFINMFAV LDELKNMKCS
VKNDHSAYKR AAQFLRKMAD PQSIQESQNL SMFLANHNKI TQSLQQQLEV ISGYEELLAD
IVNLCVDYYE NRMYLTPSEK HMLLKVMGFG LYLMDGSVSN IYKLDAKKRI NLSKIDKYFK
QLQVVPLFGD MQIELARYIK TSAHYEENKS RWTCTSSGSS PQYNICEQMI QIREDHMRFI
SELARYSNSE VVTGSGRQEA QKTDAEYRKL FDLALQGLQL LSQWSAHVME VYSWKLVHPT
DKYSNKDCPD SAEEYERATR YNYTSEEKFA LVEVIAMIKG LQVLMGRMES VFNHAIRHTV
YAALQDFSQV TLREPLRQAI KKKKNVIQSV LQAIRKTVCD WETGHEPFND PALRGEKDPK
SGFDIKVPRR AVGPSSTQLY MVRTMLESLI ADKSGSKKTL RSSLEGPTIL DIEKFHRESF
FYTHLINFSE TLQQCCDLSQ LWFREFFLEL TMGRRIQFPI EMSMPWILTD HILETKEASM
MEYVLYSLDL YNDSAHYALT RFNKQFLYDE IEAEVNLCFD QFVYKLADQI FAYYKVMAGS
LLLDKRLRSE CKNQGATIHL PPSNRYETLL KQRHVQLLGR SIDLNRLITQ RVSAAMYKSL
ELAIGRFESE DLTSIVELDG LLEINRMTHK LLSRYLTLDG FDAMFREANH NVSAPYGRIT
LHVFWELNYD FLPNYCYNGS TNRFVRTVLP FSQEFQRDKQ PNAQPQYLHG SKALNLAYSS
IYGSYRNFVG PPHFQVICRL LGYQGIAVVM EELLKVVKSL LQGTILQYVK TLMEVMPKIC
RLPRHEYGSP GILEFFHHQL KDIVEYAELK TVCFQNLREV GNAILFCLLI EQSLSLEEVC
DLLHAAPFQN ILPRVHVKEG ERLDAKMKRL ESKYAPLHLV PLIERLGTPQ QIAIAREGDL
LTKERLCCGL SMFEVILTRI RSFLDDPIWR GPLPSNGVMH VDECVEFHRL WSAMQFVYCI
PVGTHEFTVE QCFGDGLHWA GCMIIVLLGQ QRRFAVLDFC YHLLKVQKHD GKDEIIKNVP
LKKMVERIRK FQILNDEIIT ILDKYLKSGD GEGTPVEHVR CFQPPIHQSL ASS
//
ID CYFP1_HUMAN Reviewed; 1253 AA.
AC Q7L576; A8K6D9; Q14467; Q5IED0; Q6ZSX1; Q9BSD9; Q9BVC7;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 86.
DE RecName: Full=Cytoplasmic FMR1-interacting protein 1;
DE AltName: Full=Specifically Rac1-associated protein 1;
DE Short=Sra-1;
DE AltName: Full=p140sra-1;
GN Name=CYFIP1; Synonyms=KIAA0068;
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 AND 3), AND VARIANT SER-820.
RA Jiang Y.-H., Beaudet A.L.;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S.,
RA Seki N., Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II.
RT The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP SER-820.
RC TISSUE=Brain, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 50-58; 111-130; 151-163; 366-377; 441-448;
RP 505-515; 564-573; 754-760; 815-826; 867-877; 1054-1076; 1211-1224 AND
RP 1228-1240, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, and Hepatoma;
RA Bienvenut W.V., Claeys D., Boldt K., von Kriegsheim A.F., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [7]
RP FUNCTION.
RX PubMed=9417078; DOI=10.1074/jbc.273.1.291;
RA Kobayashi K., Kuroda S., Fukata M., Nakamura T., Nagase T., Nomura N.,
RA Matsuura Y., Yoshida-Kubomura N., Iwamatsu A., Kaibuchi K.;
RT "p140Sra-1 (specifically Rac1-associated protein) is a novel specific
RT target for Rac1 small GTPase.";
RL J. Biol. Chem. 273:291-295(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH DPYSL2.
RX PubMed=16260607; DOI=10.1128/MCB.25.22.9920-9935.2005;
RA Kawano Y., Yoshimura T., Tsuboi D., Kawabata S., Kaneko-Kawano T.,
RA Shirataki H., Takenawa T., Kaibuchi K.;
RT "CRMP-2 is involved in kinesin-1-dependent transport of the Sra-
RT 1/WAVE1 complex and axon formation.";
RL Mol. Cell. Biol. 25:9920-9935(2005).
RN [9]
RP FUNCTION.
RX PubMed=19524508; DOI=10.1016/j.cell.2009.04.013;
RA Silva J.M., Ezhkova E., Silva J., Heart S., Castillo M., Campos Y.,
RA Castro V., Bonilla F., Cordon-Cardo C., Muthuswamy S.K., Powers S.,
RA Fuchs E., Hannon G.J.;
RT "Cyfip1 is a putative invasion suppressor in epithelial cancers.";
RL Cell 137:1047-1061(2009).
RN [10]
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF WAVE1 COMPLEX, FUNCTION,
RP INTERACTION WITH RAC1, MUTAGENESIS OF CYS-179; ARG-190; GLU-434;
RP PHE-626; MET-632; LEU-697; TYR-704; LEU-841 AND 844-PHE-TRP-845, AND
RP SUBUNIT.
RX PubMed=21107423; DOI=10.1038/nature09623;
RA Chen Z., Borek D., Padrick S.B., Gomez T.S., Metlagel Z., Ismail A.M.,
RA Umetani J., Billadeau D.D., Otwinowski Z., Rosen M.K.;
RT "Structure and control of the actin regulatory WAVE complex.";
RL Nature 468:533-538(2010).
CC -!- FUNCTION: Component of the CYFIP1-EIF4E-FMR1 complex which binds
CC to the mRNA cap and mediates translational repression. In the
CC CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E
CC and FMR1. Promotes the translation repression activity of FMR1 in
CC brain probably by mediating its association with EIF4E and mRNA
CC (By similarity). Regulates formation of membrane ruffles and
CC lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but
CC not to RNA. Part of the WAVE complex that regulates actin filament
CC reorganization via its interaction with the Arp2/3 complex. Actin
CC remodeling activity is regulated by RAC1. Regulator of epithelial
CC morphogenesis. May act as an invasion suppressor in cancers.
CC -!- SUBUNIT: Component of the WAVE1 complex composed of ABI2, CYFIP1
CC or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a
CC heterdimer containing NCKAP1 and CYFIP1 interacts with a
CC heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the
CC CYFIP1-EIF4E-FMR1 complex which is composed of CYFIP, EIF4E and
CC FMR1. Interacts with FMR1 but does not bind to related proteins
CC FXR1 or FXR2. Interaction with EIF4E stimulates FMR1 binding.
CC Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1,
CC NCKAP1/NAP1 and WASF2/WAVE2. Interacts with the active GTP-bound
CC form of RAC1. Interacts through its C-terminus with the C-terminus
CC of DPYSL2/CRMP2 which is necessary for DPYSL2-induced axon
CC outgrowth. Interacts with NYAP1, NYAP2 and MYO16.
CC -!- INTERACTION:
CC P63073:Eif4e (xeno); NbExp=2; IntAct=EBI-1048143, EBI-2000006;
CC Q06787:FMR1; NbExp=4; IntAct=EBI-1048143, EBI-366305;
CC Q9Y2A7:NCKAP1; NbExp=3; IntAct=EBI-1048143, EBI-389845;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region (By
CC similarity). Cell projection, lamellipodium (By similarity). Cell
CC projection, ruffle (By similarity). Cell junction, synapse,
CC synaptosome (By similarity). Note=Highly expressed in the
CC perinuclear region. Enriched in synaptosomes, membrane ruffles and
CC at the tips of lamellipodia (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=3;
CC IsoId=Q7L576-1; Sequence=Displayed;
CC Name=2; Synonyms=4;
CC IsoId=Q7L576-2; Sequence=VSP_052346, VSP_052347;
CC Name=3; Synonyms=5;
CC IsoId=Q7L576-3; Sequence=VSP_052345;
CC -!- MISCELLANEOUS: Breakpoint hotspot for the Prader-Willi/Angelman
CC syndromes and may be implicated in autism. Commonly altered in
CC tumors.
CC -!- SIMILARITY: Belongs to the CYFIP family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07552.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AY763577; AAW51476.1; -; mRNA.
DR EMBL; AY763578; AAW51477.1; -; mRNA.
DR EMBL; AY763579; AAW51478.1; -; mRNA.
DR EMBL; AY763580; AAW51479.1; -; mRNA.
DR EMBL; D38549; BAA07552.1; ALT_INIT; mRNA.
DR EMBL; AK127094; BAC86825.1; -; mRNA.
DR EMBL; AK291604; BAF84293.1; -; mRNA.
DR EMBL; CH471258; EAW65555.1; -; Genomic_DNA.
DR EMBL; BC001306; AAH01306.2; -; mRNA.
DR EMBL; BC005097; AAH05097.1; -; mRNA.
DR RefSeq; NP_001028200.1; NM_001033028.1.
DR RefSeq; NP_055423.1; NM_014608.2.
DR RefSeq; XP_005272600.1; XM_005272543.1.
DR RefSeq; XP_005272601.1; XM_005272544.1.
DR UniGene; Hs.26704; -.
DR PDB; 3P8C; X-ray; 2.29 A; A=1-1253.
DR PDBsum; 3P8C; -.
DR ProteinModelPortal; Q7L576; -.
DR DIP; DIP-38873N; -.
DR IntAct; Q7L576; 20.
DR MINT; MINT-1731056; -.
DR STRING; 9606.ENSP00000324549; -.
DR PhosphoSite; Q7L576; -.
DR DMDM; 74738589; -.
DR PaxDb; Q7L576; -.
DR PRIDE; Q7L576; -.
DR DNASU; 23191; -.
DR Ensembl; ENST00000313077; ENSP00000324549; ENSG00000068793.
DR Ensembl; ENST00000435939; ENSP00000405956; ENSG00000068793.
DR Ensembl; ENST00000560848; ENSP00000454199; ENSG00000068793.
DR GeneID; 23191; -.
DR KEGG; hsa:23191; -.
DR UCSC; uc001yus.3; human.
DR CTD; 23191; -.
DR GeneCards; GC15P023873; -.
DR HGNC; HGNC:13759; CYFIP1.
DR MIM; 606322; gene.
DR neXtProt; NX_Q7L576; -.
DR Orphanet; 72; Angelman syndrome.
DR PharmGKB; PA38367; -.
DR eggNOG; NOG306641; -.
DR HOGENOM; HOG000272573; -.
DR HOVERGEN; HBG053209; -.
DR InParanoid; Q7L576; -.
DR KO; K05749; -.
DR OMA; SSNIYKL; -.
DR OrthoDB; EOG7ZSHS2; -.
DR PhylomeDB; Q7L576; -.
DR ChiTaRS; CYFIP1; human.
DR EvolutionaryTrace; Q7L576; -.
DR GeneWiki; CYFIP1; -.
DR GenomeRNAi; 23191; -.
DR NextBio; 44673; -.
DR PRO; PR:Q7L576; -.
DR ArrayExpress; Q7L576; -.
DR Bgee; Q7L576; -.
DR CleanEx; HS_CYFIP1; -.
DR Genevestigator; Q7L576; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005845; C:mRNA cap binding complex; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-KW.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0048365; F:Rac GTPase binding; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0031529; P:ruffle organization; ISS:UniProtKB.
DR InterPro; IPR008081; Cytoplasmic_FMR1-int.
DR InterPro; IPR016536; Cytoplasmic_FMR1-int_sub.
DR PANTHER; PTHR12195; PTHR12195; 1.
DR Pfam; PF05994; FragX_IP; 1.
DR PIRSF; PIRSF008153; FMR1_interacting; 1.
DR PRINTS; PR01698; CYTOFMRPINTP.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cell junction;
KW Cell projection; Cell shape; Complete proteome; Cytoplasm;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Neurogenesis; Polymorphism; Reference proteome; Synapse; Synaptosome.
FT CHAIN 1 1253 Cytoplasmic FMR1-interacting protein 1.
FT /FTId=PRO_0000279706.
FT VAR_SEQ 1 806 Missing (in isoform 3).
FT /FTId=VSP_052345.
FT VAR_SEQ 1 431 Missing (in isoform 2).
FT /FTId=VSP_052346.
FT VAR_SEQ 432 557 AEEYERATRYNYTSEEKFALVEVIAMIKGLQVLMGRMESVF
FT NHAIRHTVYAALQDFSQVTLREPLRQAIKKKKNVIQSVLQA
FT IRKTVCDWETGHEPFNDPALRGEKDPKSGFDIKVPRRAVGP
FT SST -> MAESLGSAELLRQLKSLGMERLLHAVNTFLRQSC
FT TYLPLLTFGGKTSFVSLDVYGTEANCSATSCSFPKAAATWP
FT RRQAPGPLGELVRGPPDQGVAEQSFSHGLFEFGITNVPCIF
FT SPPQMFPWII (in isoform 2).
FT /FTId=VSP_052347.
FT VARIANT 532 532 A -> P (in dbSNP:rs34683919).
FT /FTId=VAR_053849.
FT VARIANT 820 820 G -> D (in dbSNP:rs17137190).
FT /FTId=VAR_053850.
FT VARIANT 820 820 G -> S (in dbSNP:rs7170637).
FT /FTId=VAR_053851.
FT MUTAGEN 179 179 C->R: Reduced interaction with RAC1.
FT MUTAGEN 190 190 R->D: Reduced interaction with RAC1.
FT MUTAGEN 434 434 E->K: Reduced interaction with RAC1; when
FT associated with A-626.
FT MUTAGEN 626 626 F->A: Reduced interaction with RAC1; when
FT associated with K-434.
FT MUTAGEN 632 632 M->D: Reduced interaction with RAC1.
FT MUTAGEN 697 697 L->D: Constitutive induction of the
FT formation of actin filaments; when
FT associated with D-704.
FT MUTAGEN 704 704 Y->D: Constitutive induction of the
FT formation of actin filaments; when
FT associated with D-697.
FT MUTAGEN 841 841 L->A: Constitutive induction of the
FT formation of actin filaments; when
FT associated with 844-A-A-845.
FT MUTAGEN 844 845 FW->AA: Constitutive induction of the
FT formation of actin filaments; when
FT associated with A-841.
FT CONFLICT 583 583 S -> N (in Ref. 1; AAW51478 and 3;
FT BAC86825).
FT CONFLICT 898 898 Y -> H (in Ref. 1; AAW51478 and 3;
FT BAC86825).
FT CONFLICT 930 930 M -> R (in Ref. 1; AAW51478 and 3;
FT BAC86825).
FT CONFLICT 1176 1176 V -> A (in Ref. 1; AAW51479).
FT HELIX 7 17
FT HELIX 59 84
FT HELIX 90 92
FT HELIX 104 143
FT HELIX 148 150
FT HELIX 155 177
FT HELIX 179 193
FT TURN 194 196
FT HELIX 201 215
FT HELIX 219 229
FT HELIX 234 250
FT HELIX 257 274
FT STRAND 275 278
FT HELIX 281 286
FT HELIX 292 301
FT STRAND 304 308
FT STRAND 311 314
FT HELIX 316 320
FT TURN 323 325
FT HELIX 326 331
FT HELIX 346 365
FT HELIX 384 417
FT TURN 422 424
FT HELIX 434 438
FT HELIX 440 442
FT HELIX 445 467
FT HELIX 469 489
FT TURN 490 492
FT HELIX 493 501
FT HELIX 505 518
FT STRAND 522 525
FT HELIX 531 534
FT HELIX 556 570
FT TURN 580 583
FT HELIX 586 598
FT HELIX 599 601
FT HELIX 602 606
FT HELIX 608 615
FT HELIX 619 621
FT HELIX 625 630
FT TURN 631 633
FT HELIX 640 642
FT HELIX 644 655
FT HELIX 658 660
FT TURN 661 663
FT HELIX 664 668
FT HELIX 670 680
FT HELIX 685 721
FT HELIX 725 733
FT HELIX 747 750
FT STRAND 755 757
FT STRAND 760 762
FT HELIX 764 788
FT HELIX 792 794
FT HELIX 795 813
FT HELIX 821 828
FT STRAND 832 836
FT HELIX 838 849
FT HELIX 851 854
FT STRAND 855 858
FT TURN 859 862
FT STRAND 863 866
FT HELIX 869 871
FT HELIX 885 887
FT HELIX 892 901
FT HELIX 902 906
FT HELIX 911 942
FT HELIX 944 955
FT HELIX 965 967
FT HELIX 969 979
FT HELIX 981 984
FT TURN 987 992
FT HELIX 993 1025
FT HELIX 1026 1029
FT HELIX 1043 1053
FT HELIX 1055 1057
FT HELIX 1059 1066
FT HELIX 1069 1083
FT HELIX 1086 1088
FT STRAND 1090 1092
FT HELIX 1093 1101
FT TURN 1107 1110
FT STRAND 1121 1123
FT HELIX 1127 1139
FT HELIX 1149 1153
FT HELIX 1156 1167
FT HELIX 1171 1177
FT HELIX 1179 1190
FT HELIX 1201 1225
SQ SEQUENCE 1253 AA; 145182 MW; D8F45E13207BEF16 CRC64;
MAAQVTLEDA LSNVDLLEEL PLPDQQPCIE PPPSSLLYQP NFNTNFEDRN AFVTGIARYI
EQATVHSSMN EMLEEGQEYA VMLYTWRSCS RAIPQVKCNE QPNRVEIYEK TVEVLEPEVT
KLMNFMYFQR NAIERFCGEV RRLCHAERRK DFVSEAYLIT LGKFINMFAV LDELKNMKCS
VKNDHSAYKR AAQFLRKMAD PQSIQESQNL SMFLANHNKI TQSLQQQLEV ISGYEELLAD
IVNLCVDYYE NRMYLTPSEK HMLLKVMGFG LYLMDGSVSN IYKLDAKKRI NLSKIDKYFK
QLQVVPLFGD MQIELARYIK TSAHYEENKS RWTCTSSGSS PQYNICEQMI QIREDHMRFI
SELARYSNSE VVTGSGRQEA QKTDAEYRKL FDLALQGLQL LSQWSAHVME VYSWKLVHPT
DKYSNKDCPD SAEEYERATR YNYTSEEKFA LVEVIAMIKG LQVLMGRMES VFNHAIRHTV
YAALQDFSQV TLREPLRQAI KKKKNVIQSV LQAIRKTVCD WETGHEPFND PALRGEKDPK
SGFDIKVPRR AVGPSSTQLY MVRTMLESLI ADKSGSKKTL RSSLEGPTIL DIEKFHRESF
FYTHLINFSE TLQQCCDLSQ LWFREFFLEL TMGRRIQFPI EMSMPWILTD HILETKEASM
MEYVLYSLDL YNDSAHYALT RFNKQFLYDE IEAEVNLCFD QFVYKLADQI FAYYKVMAGS
LLLDKRLRSE CKNQGATIHL PPSNRYETLL KQRHVQLLGR SIDLNRLITQ RVSAAMYKSL
ELAIGRFESE DLTSIVELDG LLEINRMTHK LLSRYLTLDG FDAMFREANH NVSAPYGRIT
LHVFWELNYD FLPNYCYNGS TNRFVRTVLP FSQEFQRDKQ PNAQPQYLHG SKALNLAYSS
IYGSYRNFVG PPHFQVICRL LGYQGIAVVM EELLKVVKSL LQGTILQYVK TLMEVMPKIC
RLPRHEYGSP GILEFFHHQL KDIVEYAELK TVCFQNLREV GNAILFCLLI EQSLSLEEVC
DLLHAAPFQN ILPRVHVKEG ERLDAKMKRL ESKYAPLHLV PLIERLGTPQ QIAIAREGDL
LTKERLCCGL SMFEVILTRI RSFLDDPIWR GPLPSNGVMH VDECVEFHRL WSAMQFVYCI
PVGTHEFTVE QCFGDGLHWA GCMIIVLLGQ QRRFAVLDFC YHLLKVQKHD GKDEIIKNVP
LKKMVERIRK FQILNDEIIT ILDKYLKSGD GEGTPVEHVR CFQPPIHQSL ASS
//
MIM
606322
*RECORD*
*FIELD* NO
606322
*FIELD* TI
*606322 CYTOPLASMIC FMRP-INTERACTING PROTEIN 1; CYFIP1
;;SPECIFICALLY RAC1-ASSOCIATED PROTEIN 1; SRA1;;
read moreKIAA0068
*FIELD* TX
CLONING
By sequencing clones obtained from an immature myeloid cell line (KG-1)
cDNA library, Nomura et al. (1994) cloned CYFIP1, which they designated
KIAA0068. The deduced protein contains 1,271 amino acids. Northern blot
analysis detected CYFIP1 expression in all human tissues and cell lines
examined. Highest expression was in lung, kidney, spleen, prostate, and
ovary, as well as in HeLa cells and KG-1 cells.
To identify novel proteins that interact with the fragile X mental
retardation protein (FMRP), encoded by the FMR1 gene (309550), Schenck
et al. (2001) used yeast 2-hybrid screening with the FMRP N terminus as
bait. They identified 2 proteins as FMRP interactors, CYFIP1 and CYFIP2
(606323). CYFIP1 contains 1,253 amino acids and shares 88% sequence
identity with CYFIP2. CYFIP1 and CYFIP2 are members of a highly
conserved protein family and share approximately 99% sequence identity
with their mouse orthologs.
By genomic sequence analysis to identify novel genes adjacent to the
imprinted domain in the Prader-Willi syndrome (PWS; 176270)/Angelman
(AS; 105830) syndrome deletion region of chromosome 15, Chai et al.
(2003) identified CYFIP1. Northern blot analysis detected a 4.4-kb
transcript in all human and mouse tissues examined, with highest
expression in placenta.
GENE FUNCTION
Schenck et al. (2001) found that CYFIP1 interacts exclusively with FMRP,
whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P
(600819) and FXR2P (605339). The interaction of FMRP and CYFIP involves
the domain of FMRP that also mediates homo- and heteromerization,
suggesting a competition between interaction among the FXR proteins and
interaction with CYFIP. Schenck et al. (2001) determined that CYFIP1 and
CYFIP2 are distributed in an identical pattern in the cytoplasm, showing
colocalization with FMRP and ribosomes. CYFIP1 has been shown to
interact with the small GTPase RAC1 (602048), which is implicated in
development and maintenance of neuronal structures (Kobayashi et al.,
1998). Consistent with FMRP and RAC1 localization in dendritic fine
structures, CYFIP1/2 are present in synaptosomal extracts.
RAC1 stimulates actin remodeling at the cell periphery, leading to
lamellipodia formation. Steffen et al. (2004) found that Sra1 and Nap1
(NCKAP1; 604891) interacted with Wave2 (WASF2; 605875) and Abi1
(SSH3BP1; 603050) in resting mouse melanoma cells or following Rac1
activation. Microinjection of constitutively active RAC1 resulted in
translocation of Sra1, Nap1, Wave2, and Abi1 to the tips of membrane
protrusions. Moreover, removal of SRA1 or NAP1 by RNA interference in
human or mouse cells abrogated formation of RAC1-dependent lamellipodia.
Microinjection of active RAC1 failed to restore lamellipodia protrusion
in cells lacking either SRA1 or NAP1. Steffen et al. (2004) concluded
that SRA1 and NAP1 are essential components of a WAVE2- and
ABI1-containing complex linking RAC1 to site-directed actin assembly.
GENE STRUCTURE
Chai et al. (2003) determined that the CYFIP1 gene contains 31 exons and
spans 111.4 kb. The 5-prime end is associated with a strong CpG island.
The mouse Cyfip1 gene has a similar 31-exon structure.
MAPPING
By analysis of a panel of human-rodent hybrid cell lines, Nomura et al.
(1994) mapped the CYFIP1 gene to chromosome 15.
By genomic sequence analysis, Chai et al. (2003) mapped the CYFIP1 gene
to chromosome 15q11.2, within a region deleted in some cases of PWS and
AS. CYFIP1 lies within a gene cluster distal to breakpoint hotspot 1
(BP1) and proximal to BP2. The order of genes within this cluster is
cen-NIPA1 (608145)-NIPA2 (608146)-CYFIP1-GCP5 (608147)-BP2-tel. Chai et
al. (2003) mapped the mouse Cyfip1 gene to a region of chromosome 7C
that contains the same gene cluster and shows homology of synteny to
human chromosome 15q11-q13.
MOLECULAR GENETICS
Deletions associated with AS and PWS are either class I, with the
deletion extending from BP1 (15q11.2) to BP3 (15q13), or class II, with
a more telomeric deletion extending from BP2 (15q11.2) to BP3. Chai et
al. (2003) determined that a BAC clone containing exons 7 through 31 of
the CYFIP1 gene, which is located between BP1 and BP2, could be used as
probe in FISH to distinguish between class I and class II deletions in a
panel of cell lines from patients with AS deletions.
By replication-timing studies, Chai et al. (2003) determined that
replication of the mouse genomic region spanning Nipa1-Nipa2-Cyfip1
showed a pattern of asynchrony, but the asynchrony was not due to
parent-of-origin influences. PCR of mouse brain cDNA from transgenic PWS
and AS mouse models indicated that the Nipa1, Nipa2, Cyfip1, and Gcp5
genes are nonimprinted. RT-PCR detected expression of the human NIPA1,
NIPA2, CYFIP1, and GCP5 genes in lymphocytes from a normal individual
and from PWS and AS imprinting mutation patients. CYFIP1 was expressed
from both the maternal and paternal chromosome 15 in somatic cell
hybrids, further indicating that these 4 genes are nonimprinted.
*FIELD* RF
1. Chai, J.-H.; Locke, D. P.; Greally, J. M.; Knoll, J. H. M.; Ohta,
T.; Dunai, J.; Yavor, A.; Eichler, E. E.; Nicholls, R. D.: Identification
of four highly conserved genes between breakpoint hotspots BP1 and
BP2 of the Prader-Willi/Angelman syndromes deletion region that have
undergone evolutionary transposition mediated by flanking duplicons. Am.
J. Hum. Genet. 73: 898-925, 2003.
2. Kobayashi, K.; Kuroda, S.; Fukata, M.; Nakamura, T.; Nagase, T.;
Nomura, N.; Matsuura, Y.; Yoshida-Kubomura, N.; Iwamatsu, A.; Kaibuchi,
K.: p140Sra-1 (specifically Rac1-associated protein) is a novel specific
target for Rac1 small GTPase. J. Biol. Chem. 273: 291-295, 1998.
3. Nomura, N.; Nagase, T.; Miyajima, N.; Sazuka, T.; Tanaka, A.; Sato,
S.; Seki, N.; Kawarabayasi, Y.; Ishikawa, K.; Tabata, S.: Prediction
of the coding sequences of unidentified human genes. II. The coding
sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis
of cDNA clones from human cell line KG-1. DNA Res. 1: 223-229, 1994.
4. Schenck, A.; Bardoni, B.; Moro, A.; Bagni, C.; Mandel, J. L.:
A highly conserved protein family interacting with the fragile X mental
retardation protein (FMRP) and displaying selective interactions with
FMRP-related proteins FXR1P and FXR2P. Proc. Nat. Acad. Sci. 98:
8844-8849, 2001.
5. Steffen, A.; Rottner, K.; Ehinger, J.; Innocenti, M.; Scita, G.;
Wehland, J.; Stradal, T. E. B.: Sra-1 and Nap1 link Rac to actin
assembly driving lamellipodia formation. EMBO J. 23: 749-759, 2004.
*FIELD* CN
Patricia A. Hartz - updated: 2/23/2006
Patricia A. Hartz - updated: 10/2/2003
*FIELD* CD
Victor A. McKusick: 9/28/2001
*FIELD* ED
alopez: 07/23/2013
carol: 3/26/2013
wwang: 4/10/2009
mgross: 3/2/2006
terry: 2/23/2006
alopez: 3/19/2004
mgross: 10/2/2003
mcapotos: 12/26/2001
carol: 9/28/2001
*RECORD*
*FIELD* NO
606322
*FIELD* TI
*606322 CYTOPLASMIC FMRP-INTERACTING PROTEIN 1; CYFIP1
;;SPECIFICALLY RAC1-ASSOCIATED PROTEIN 1; SRA1;;
read moreKIAA0068
*FIELD* TX
CLONING
By sequencing clones obtained from an immature myeloid cell line (KG-1)
cDNA library, Nomura et al. (1994) cloned CYFIP1, which they designated
KIAA0068. The deduced protein contains 1,271 amino acids. Northern blot
analysis detected CYFIP1 expression in all human tissues and cell lines
examined. Highest expression was in lung, kidney, spleen, prostate, and
ovary, as well as in HeLa cells and KG-1 cells.
To identify novel proteins that interact with the fragile X mental
retardation protein (FMRP), encoded by the FMR1 gene (309550), Schenck
et al. (2001) used yeast 2-hybrid screening with the FMRP N terminus as
bait. They identified 2 proteins as FMRP interactors, CYFIP1 and CYFIP2
(606323). CYFIP1 contains 1,253 amino acids and shares 88% sequence
identity with CYFIP2. CYFIP1 and CYFIP2 are members of a highly
conserved protein family and share approximately 99% sequence identity
with their mouse orthologs.
By genomic sequence analysis to identify novel genes adjacent to the
imprinted domain in the Prader-Willi syndrome (PWS; 176270)/Angelman
(AS; 105830) syndrome deletion region of chromosome 15, Chai et al.
(2003) identified CYFIP1. Northern blot analysis detected a 4.4-kb
transcript in all human and mouse tissues examined, with highest
expression in placenta.
GENE FUNCTION
Schenck et al. (2001) found that CYFIP1 interacts exclusively with FMRP,
whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P
(600819) and FXR2P (605339). The interaction of FMRP and CYFIP involves
the domain of FMRP that also mediates homo- and heteromerization,
suggesting a competition between interaction among the FXR proteins and
interaction with CYFIP. Schenck et al. (2001) determined that CYFIP1 and
CYFIP2 are distributed in an identical pattern in the cytoplasm, showing
colocalization with FMRP and ribosomes. CYFIP1 has been shown to
interact with the small GTPase RAC1 (602048), which is implicated in
development and maintenance of neuronal structures (Kobayashi et al.,
1998). Consistent with FMRP and RAC1 localization in dendritic fine
structures, CYFIP1/2 are present in synaptosomal extracts.
RAC1 stimulates actin remodeling at the cell periphery, leading to
lamellipodia formation. Steffen et al. (2004) found that Sra1 and Nap1
(NCKAP1; 604891) interacted with Wave2 (WASF2; 605875) and Abi1
(SSH3BP1; 603050) in resting mouse melanoma cells or following Rac1
activation. Microinjection of constitutively active RAC1 resulted in
translocation of Sra1, Nap1, Wave2, and Abi1 to the tips of membrane
protrusions. Moreover, removal of SRA1 or NAP1 by RNA interference in
human or mouse cells abrogated formation of RAC1-dependent lamellipodia.
Microinjection of active RAC1 failed to restore lamellipodia protrusion
in cells lacking either SRA1 or NAP1. Steffen et al. (2004) concluded
that SRA1 and NAP1 are essential components of a WAVE2- and
ABI1-containing complex linking RAC1 to site-directed actin assembly.
GENE STRUCTURE
Chai et al. (2003) determined that the CYFIP1 gene contains 31 exons and
spans 111.4 kb. The 5-prime end is associated with a strong CpG island.
The mouse Cyfip1 gene has a similar 31-exon structure.
MAPPING
By analysis of a panel of human-rodent hybrid cell lines, Nomura et al.
(1994) mapped the CYFIP1 gene to chromosome 15.
By genomic sequence analysis, Chai et al. (2003) mapped the CYFIP1 gene
to chromosome 15q11.2, within a region deleted in some cases of PWS and
AS. CYFIP1 lies within a gene cluster distal to breakpoint hotspot 1
(BP1) and proximal to BP2. The order of genes within this cluster is
cen-NIPA1 (608145)-NIPA2 (608146)-CYFIP1-GCP5 (608147)-BP2-tel. Chai et
al. (2003) mapped the mouse Cyfip1 gene to a region of chromosome 7C
that contains the same gene cluster and shows homology of synteny to
human chromosome 15q11-q13.
MOLECULAR GENETICS
Deletions associated with AS and PWS are either class I, with the
deletion extending from BP1 (15q11.2) to BP3 (15q13), or class II, with
a more telomeric deletion extending from BP2 (15q11.2) to BP3. Chai et
al. (2003) determined that a BAC clone containing exons 7 through 31 of
the CYFIP1 gene, which is located between BP1 and BP2, could be used as
probe in FISH to distinguish between class I and class II deletions in a
panel of cell lines from patients with AS deletions.
By replication-timing studies, Chai et al. (2003) determined that
replication of the mouse genomic region spanning Nipa1-Nipa2-Cyfip1
showed a pattern of asynchrony, but the asynchrony was not due to
parent-of-origin influences. PCR of mouse brain cDNA from transgenic PWS
and AS mouse models indicated that the Nipa1, Nipa2, Cyfip1, and Gcp5
genes are nonimprinted. RT-PCR detected expression of the human NIPA1,
NIPA2, CYFIP1, and GCP5 genes in lymphocytes from a normal individual
and from PWS and AS imprinting mutation patients. CYFIP1 was expressed
from both the maternal and paternal chromosome 15 in somatic cell
hybrids, further indicating that these 4 genes are nonimprinted.
*FIELD* RF
1. Chai, J.-H.; Locke, D. P.; Greally, J. M.; Knoll, J. H. M.; Ohta,
T.; Dunai, J.; Yavor, A.; Eichler, E. E.; Nicholls, R. D.: Identification
of four highly conserved genes between breakpoint hotspots BP1 and
BP2 of the Prader-Willi/Angelman syndromes deletion region that have
undergone evolutionary transposition mediated by flanking duplicons. Am.
J. Hum. Genet. 73: 898-925, 2003.
2. Kobayashi, K.; Kuroda, S.; Fukata, M.; Nakamura, T.; Nagase, T.;
Nomura, N.; Matsuura, Y.; Yoshida-Kubomura, N.; Iwamatsu, A.; Kaibuchi,
K.: p140Sra-1 (specifically Rac1-associated protein) is a novel specific
target for Rac1 small GTPase. J. Biol. Chem. 273: 291-295, 1998.
3. Nomura, N.; Nagase, T.; Miyajima, N.; Sazuka, T.; Tanaka, A.; Sato,
S.; Seki, N.; Kawarabayasi, Y.; Ishikawa, K.; Tabata, S.: Prediction
of the coding sequences of unidentified human genes. II. The coding
sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis
of cDNA clones from human cell line KG-1. DNA Res. 1: 223-229, 1994.
4. Schenck, A.; Bardoni, B.; Moro, A.; Bagni, C.; Mandel, J. L.:
A highly conserved protein family interacting with the fragile X mental
retardation protein (FMRP) and displaying selective interactions with
FMRP-related proteins FXR1P and FXR2P. Proc. Nat. Acad. Sci. 98:
8844-8849, 2001.
5. Steffen, A.; Rottner, K.; Ehinger, J.; Innocenti, M.; Scita, G.;
Wehland, J.; Stradal, T. E. B.: Sra-1 and Nap1 link Rac to actin
assembly driving lamellipodia formation. EMBO J. 23: 749-759, 2004.
*FIELD* CN
Patricia A. Hartz - updated: 2/23/2006
Patricia A. Hartz - updated: 10/2/2003
*FIELD* CD
Victor A. McKusick: 9/28/2001
*FIELD* ED
alopez: 07/23/2013
carol: 3/26/2013
wwang: 4/10/2009
mgross: 3/2/2006
terry: 2/23/2006
alopez: 3/19/2004
mgross: 10/2/2003
mcapotos: 12/26/2001
carol: 9/28/2001