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Protein

Cytoplasmic FMR1-interacting protein 1

Gene

CYFIP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). May act as an invasion suppressor in cancers.By similarity4 Publications

Miscellaneous

Breakpoint hotspot for the Prader-Willi/Angelman syndromes and may be implicated in autism. Commonly altered in tumors.

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • protein-containing complex binding Source: UniProtKB
  • Rac GTPase binding Source: UniProtKB
  • RNA 7-methylguanosine cap binding Source: GO_Central
  • translation regulator activity Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionActin-binding, Developmental protein
Biological processCell shape, Differentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-6798695 Neutrophil degranulation
SIGNORiQ7L576

Names & Taxonomyi

Protein namesi
Recommended name:
Cytoplasmic FMR1-interacting protein 1
Alternative name(s):
Specifically Rac1-associated protein 1
Short name:
Sra-1
p140sra-1
Gene namesi
Name:CYFIP1Imported
Synonyms:KIAA0068Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000273749.4
HGNCiHGNC:13759 CYFIP1
MIMi606322 gene
neXtProtiNX_Q7L576

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Synapse, Synaptosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi179C → R: Reduced interaction with RAC1. 1 Publication1
Mutagenesisi190R → D: Reduced interaction with RAC1. 1 Publication1
Mutagenesisi434E → K: Reduced interaction with RAC1; when associated with A-626. 1 Publication1
Mutagenesisi626F → A: Reduced interaction with RAC1; when associated with K-434. 1 Publication1
Mutagenesisi632M → D: Reduced interaction with RAC1. 1 Publication1
Mutagenesisi697L → D: Constitutive induction of the formation of actin filaments; when associated with D-704. 1 Publication1
Mutagenesisi704Y → D: Constitutive induction of the formation of actin filaments; when associated with D-697. 1 Publication1
Mutagenesisi841L → A: Constitutive induction of the formation of actin filaments; when associated with 844-A-A-845. 1 Publication1
Mutagenesisi844 – 845FW → AA: Constitutive induction of the formation of actin filaments; when associated with A-841. 1 Publication2

Organism-specific databases

DisGeNETi23191
OpenTargetsiENSG00000273749
PharmGKBiPA38367

Polymorphism and mutation databases

BioMutaiCYFIP1
DMDMi74738589

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002797061 – 1253Cytoplasmic FMR1-interacting protein 1Add BLAST1253

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei583PhosphoserineCombined sources1
Modified residuei1234PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ7L576
MaxQBiQ7L576
PaxDbiQ7L576
PeptideAtlasiQ7L576
PRIDEiQ7L576
ProteomicsDBi68792
68793 [Q7L576-2]
68794 [Q7L576-3]

PTM databases

GlyConnecti1168
iPTMnetiQ7L576
PhosphoSitePlusiQ7L576
SwissPalmiQ7L576

Expressioni

Gene expression databases

BgeeiENSG00000273749 Expressed in 233 organ(s), highest expression level in epithelium of mammary gland
CleanExiHS_CYFIP1
ExpressionAtlasiQ7L576 baseline and differential
GenevisibleiQ7L576 HS

Organism-specific databases

HPAiHPA068106

Interactioni

Subunit structurei

Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the CYFIP1-EIF4E-FMR1 complex which is composed of CYFIP, EIF4E and FMR1. Interacts with FMR1 but does not bind to related proteins FXR1 or FXR2. Interaction with EIF4E stimulates FMR1 binding. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2 (PubMed:16417406). Interacts with the active GTP-bound form of RAC1. Interacts through its C-terminus with the C-terminus of DPYSL2/CRMP2 which is necessary for DPYSL2-induced axon outgrowth. Interacts with NYAP1, NYAP2 and MYO16. Interacts with TMEM108 (via N-terminus); the interaction associates TMEM108 with the WAVE1 complex (By similarity).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116800, 70 interactors
CORUMiQ7L576
DIPiDIP-38873N
IntActiQ7L576, 49 interactors
MINTiQ7L576
STRINGi9606.ENSP00000324549

Structurei

Secondary structure

11253
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ7L576
SMRiQ7L576
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ7L576

Family & Domainsi

Sequence similaritiesi

Belongs to the CYFIP family.Sequence analysis

Phylogenomic databases

eggNOGiKOG3534 Eukaryota
ENOG410XPKW LUCA
GeneTreeiENSGT00500000044831
HOGENOMiHOG000272573
HOVERGENiHBG053209
InParanoidiQ7L576
KOiK05749
OMAiSAHFEEN
OrthoDBiEOG091G0105
PhylomeDBiQ7L576
TreeFamiTF312925

Family and domain databases

InterProiView protein in InterPro
IPR008081 Cytoplasmic_FMR1-int
IPR009828 DUF1394
PANTHERiPTHR12195 PTHR12195, 1 hit
PfamiView protein in Pfam
PF07159 DUF1394, 1 hit
PF05994 FragX_IP, 1 hit
PIRSFiPIRSF008153 FMR1_interacting, 1 hit
PRINTSiPR01698 CYTOFMRPINTP

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q7L576-1) [UniParc]FASTAAdd to basket
Also known as: 3

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAAQVTLEDA LSNVDLLEEL PLPDQQPCIE PPPSSLLYQP NFNTNFEDRN
60 70 80 90 100
AFVTGIARYI EQATVHSSMN EMLEEGQEYA VMLYTWRSCS RAIPQVKCNE
110 120 130 140 150
QPNRVEIYEK TVEVLEPEVT KLMNFMYFQR NAIERFCGEV RRLCHAERRK
160 170 180 190 200
DFVSEAYLIT LGKFINMFAV LDELKNMKCS VKNDHSAYKR AAQFLRKMAD
210 220 230 240 250
PQSIQESQNL SMFLANHNKI TQSLQQQLEV ISGYEELLAD IVNLCVDYYE
260 270 280 290 300
NRMYLTPSEK HMLLKVMGFG LYLMDGSVSN IYKLDAKKRI NLSKIDKYFK
310 320 330 340 350
QLQVVPLFGD MQIELARYIK TSAHYEENKS RWTCTSSGSS PQYNICEQMI
360 370 380 390 400
QIREDHMRFI SELARYSNSE VVTGSGRQEA QKTDAEYRKL FDLALQGLQL
410 420 430 440 450
LSQWSAHVME VYSWKLVHPT DKYSNKDCPD SAEEYERATR YNYTSEEKFA
460 470 480 490 500
LVEVIAMIKG LQVLMGRMES VFNHAIRHTV YAALQDFSQV TLREPLRQAI
510 520 530 540 550
KKKKNVIQSV LQAIRKTVCD WETGHEPFND PALRGEKDPK SGFDIKVPRR
560 570 580 590 600
AVGPSSTQLY MVRTMLESLI ADKSGSKKTL RSSLEGPTIL DIEKFHRESF
610 620 630 640 650
FYTHLINFSE TLQQCCDLSQ LWFREFFLEL TMGRRIQFPI EMSMPWILTD
660 670 680 690 700
HILETKEASM MEYVLYSLDL YNDSAHYALT RFNKQFLYDE IEAEVNLCFD
710 720 730 740 750
QFVYKLADQI FAYYKVMAGS LLLDKRLRSE CKNQGATIHL PPSNRYETLL
760 770 780 790 800
KQRHVQLLGR SIDLNRLITQ RVSAAMYKSL ELAIGRFESE DLTSIVELDG
810 820 830 840 850
LLEINRMTHK LLSRYLTLDG FDAMFREANH NVSAPYGRIT LHVFWELNYD
860 870 880 890 900
FLPNYCYNGS TNRFVRTVLP FSQEFQRDKQ PNAQPQYLHG SKALNLAYSS
910 920 930 940 950
IYGSYRNFVG PPHFQVICRL LGYQGIAVVM EELLKVVKSL LQGTILQYVK
960 970 980 990 1000
TLMEVMPKIC RLPRHEYGSP GILEFFHHQL KDIVEYAELK TVCFQNLREV
1010 1020 1030 1040 1050
GNAILFCLLI EQSLSLEEVC DLLHAAPFQN ILPRVHVKEG ERLDAKMKRL
1060 1070 1080 1090 1100
ESKYAPLHLV PLIERLGTPQ QIAIAREGDL LTKERLCCGL SMFEVILTRI
1110 1120 1130 1140 1150
RSFLDDPIWR GPLPSNGVMH VDECVEFHRL WSAMQFVYCI PVGTHEFTVE
1160 1170 1180 1190 1200
QCFGDGLHWA GCMIIVLLGQ QRRFAVLDFC YHLLKVQKHD GKDEIIKNVP
1210 1220 1230 1240 1250
LKKMVERIRK FQILNDEIIT ILDKYLKSGD GEGTPVEHVR CFQPPIHQSL

ASS
Length:1,253
Mass (Da):145,182
Last modified:July 5, 2004 - v1
Checksum:iD8F45E13207BEF16
GO
Isoform 2 (identifier: Q7L576-2) [UniParc]FASTAAdd to basket
Also known as: 4

The sequence of this isoform differs from the canonical sequence as follows:
     1-431: Missing.
     432-557: AEEYERATRY...PRRAVGPSST → MAESLGSAEL...SPPQMFPWII

Show »
Length:822
Mass (Da):94,467
Checksum:i035E45763DC5F6C4
GO
Isoform 3 (identifier: Q7L576-3) [UniParc]FASTAAdd to basket
Also known as: 5

The sequence of this isoform differs from the canonical sequence as follows:
     1-806: Missing.

Show »
Length:447
Mass (Da):51,534
Checksum:i1D9F2A088E5891A2
GO

Computationally mapped potential isoform sequencesi

There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YL50H0YL50_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
176Annotation score:
A0A087WVZ5A0A087WVZ5_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
185Annotation score:
A0A087WZ89A0A087WZ89_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
45Annotation score:
A0A087WWL1A0A087WWL1_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
161Annotation score:
A0A087WU52A0A087WU52_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
151Annotation score:
A0A087WWY5A0A087WWY5_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
77Annotation score:
A0A0G2JQT1A0A0G2JQT1_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
862Annotation score:
A0A0G2JR96A0A0G2JR96_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
862Annotation score:
A0A0G2JQH3A0A0G2JQH3_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
185Annotation score:
A0A0G2JRF5A0A0G2JRF5_HUMAN
Cytoplasmic FMR1-interacting protei...
CYFIP1
77Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence BAA07552 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti583S → N in AAW51478 (Ref. 1) Curated1
Sequence conflicti583S → N in BAC86825 (PubMed:14702039).Curated1
Sequence conflicti898Y → H in AAW51478 (Ref. 1) Curated1
Sequence conflicti898Y → H in BAC86825 (PubMed:14702039).Curated1
Sequence conflicti930M → R in AAW51478 (Ref. 1) Curated1
Sequence conflicti930M → R in BAC86825 (PubMed:14702039).Curated1
Sequence conflicti1176V → A in AAW51479 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053849532A → P. Corresponds to variant dbSNP:rs34683919Ensembl.1
Natural variantiVAR_053850820G → D. Corresponds to variant dbSNP:rs17137190Ensembl.1
Natural variantiVAR_053851820G → S2 PublicationsCorresponds to variant dbSNP:rs7170637Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0523451 – 806Missing in isoform 3. 1 PublicationAdd BLAST806
Alternative sequenceiVSP_0523461 – 431Missing in isoform 2. 2 PublicationsAdd BLAST431
Alternative sequenceiVSP_052347432 – 557AEEYE…GPSST → MAESLGSAELLRQLKSLGME RLLHAVNTFLRQSCTYLPLL TFGGKTSFVSLDVYGTEANC SATSCSFPKAAATWPRRQAP GPLGELVRGPPDQGVAEQSF SHGLFEFGITNVPCIFSPPQ MFPWII in isoform 2. 2 PublicationsAdd BLAST126

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY763577 mRNA Translation: AAW51476.1
AY763578 mRNA Translation: AAW51477.1
AY763579 mRNA Translation: AAW51478.1
AY763580 mRNA Translation: AAW51479.1
D38549 mRNA Translation: BAA07552.1 Different initiation.
AK127094 mRNA Translation: BAC86825.1
AK291604 mRNA Translation: BAF84293.1
CH471258 Genomic DNA Translation: EAW65555.1
BC001306 mRNA Translation: AAH01306.2
BC005097 mRNA Translation: AAH05097.1
CCDSiCCDS73695.1 [Q7L576-2]
CCDS73696.1 [Q7L576-1]
RefSeqiNP_001028200.1, NM_001033028.1 [Q7L576-2]
NP_001274739.1, NM_001287810.2 [Q7L576-1]
NP_001311049.1, NM_001324120.1 [Q7L576-1]
NP_001311052.1, NM_001324123.1 [Q7L576-1]
NP_055423.1, NM_014608.4 [Q7L576-1]
UniGeneiHs.26704

Genome annotation databases

EnsembliENST00000610365; ENSP00000478779; ENSG00000273749 [Q7L576-1]
ENST00000617556; ENSP00000480525; ENSG00000273749 [Q7L576-2]
ENST00000617928; ENSP00000481038; ENSG00000273749 [Q7L576-1]
GeneIDi23191
KEGGihsa:23191
UCSCiuc001yus.5 human [Q7L576-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY763577 mRNA Translation: AAW51476.1
AY763578 mRNA Translation: AAW51477.1
AY763579 mRNA Translation: AAW51478.1
AY763580 mRNA Translation: AAW51479.1
D38549 mRNA Translation: BAA07552.1 Different initiation.
AK127094 mRNA Translation: BAC86825.1
AK291604 mRNA Translation: BAF84293.1
CH471258 Genomic DNA Translation: EAW65555.1
BC001306 mRNA Translation: AAH01306.2
BC005097 mRNA Translation: AAH05097.1
CCDSiCCDS73695.1 [Q7L576-2]
CCDS73696.1 [Q7L576-1]
RefSeqiNP_001028200.1, NM_001033028.1 [Q7L576-2]
NP_001274739.1, NM_001287810.2 [Q7L576-1]
NP_001311049.1, NM_001324120.1 [Q7L576-1]
NP_001311052.1, NM_001324123.1 [Q7L576-1]
NP_055423.1, NM_014608.4 [Q7L576-1]
UniGeneiHs.26704

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P8CX-ray2.29A1-1253[»]
4N78X-ray2.43A1-1253[»]
ProteinModelPortaliQ7L576
SMRiQ7L576
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116800, 70 interactors
CORUMiQ7L576
DIPiDIP-38873N
IntActiQ7L576, 49 interactors
MINTiQ7L576
STRINGi9606.ENSP00000324549

PTM databases

GlyConnecti1168
iPTMnetiQ7L576
PhosphoSitePlusiQ7L576
SwissPalmiQ7L576

Polymorphism and mutation databases

BioMutaiCYFIP1
DMDMi74738589

Proteomic databases

EPDiQ7L576
MaxQBiQ7L576
PaxDbiQ7L576
PeptideAtlasiQ7L576
PRIDEiQ7L576
ProteomicsDBi68792
68793 [Q7L576-2]
68794 [Q7L576-3]

Protocols and materials databases

DNASUi23191
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000610365; ENSP00000478779; ENSG00000273749 [Q7L576-1]
ENST00000617556; ENSP00000480525; ENSG00000273749 [Q7L576-2]
ENST00000617928; ENSP00000481038; ENSG00000273749 [Q7L576-1]
GeneIDi23191
KEGGihsa:23191
UCSCiuc001yus.5 human [Q7L576-1]

Organism-specific databases

CTDi23191
DisGeNETi23191
EuPathDBiHostDB:ENSG00000273749.4
GeneCardsiCYFIP1
HGNCiHGNC:13759 CYFIP1
HPAiHPA068106
MIMi606322 gene
neXtProtiNX_Q7L576
OpenTargetsiENSG00000273749
PharmGKBiPA38367
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3534 Eukaryota
ENOG410XPKW LUCA
GeneTreeiENSGT00500000044831
HOGENOMiHOG000272573
HOVERGENiHBG053209
InParanoidiQ7L576
KOiK05749
OMAiSAHFEEN
OrthoDBiEOG091G0105
PhylomeDBiQ7L576
TreeFamiTF312925

Enzyme and pathway databases

ReactomeiR-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-6798695 Neutrophil degranulation
SIGNORiQ7L576

Miscellaneous databases

ChiTaRSiCYFIP1 human
EvolutionaryTraceiQ7L576
GeneWikiiCYFIP1
GenomeRNAii23191
PROiPR:Q7L576
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000273749 Expressed in 233 organ(s), highest expression level in epithelium of mammary gland
CleanExiHS_CYFIP1
ExpressionAtlasiQ7L576 baseline and differential
GenevisibleiQ7L576 HS

Family and domain databases

InterProiView protein in InterPro
IPR008081 Cytoplasmic_FMR1-int
IPR009828 DUF1394
PANTHERiPTHR12195 PTHR12195, 1 hit
PfamiView protein in Pfam
PF07159 DUF1394, 1 hit
PF05994 FragX_IP, 1 hit
PIRSFiPIRSF008153 FMR1_interacting, 1 hit
PRINTSiPR01698 CYTOFMRPINTP
ProtoNetiSearch...

Entry informationi

Entry nameiCYFP1_HUMAN
AccessioniPrimary (citable) accession number: Q7L576
Secondary accession number(s): A8K6D9
, Q14467, Q5IED0, Q6ZSX1, Q9BSD9, Q9BVC7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: July 5, 2004
Last modified: November 7, 2018
This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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