Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O95466 (FMNL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Formin-like protein 1
Alternative name(s):
CLL-associated antigen KW-13
Leukocyte formin
Gene names
Name:FMNL1
Synonyms:C17orf1, C17orf1B, FMNL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1100 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in the control of cell motility and survival of macrophages By similarity. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape. Ref.13

Subunit structure

Interacts with RAC1, PFN1 and PFN2 By similarity. Interacts (activated by RAC1) with SRGAP2 (via SH3 domain); regulates the actin filament severing activity of FMNL1. Ref.15

Subcellular location

Cytoplasm By similarity. Cell membrane; Lipid-anchor. Cytoplasmic vesiclephagosome By similarity. Note: Recruited to actin-rich phagosomes during phagocytosis. Translocates to the plasma membrane upon activation by RAC1 By similarity. Ref.7

Isoform 3: Cytoplasmcell cortex. Cell projectionbleb. Note: Colocalized with F-actin in bleb protrusions. Ref.7

Tissue specificity

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Domain

The DAD domain regulates activation via by an autoinhibitory interaction with the N-terminus. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments By similarity.

Post-translational modification

Myristoylation mediates membrane localization and blebbing.

Sequence similarities

Belongs to the formin homology family.

Contains 1 DAD (diaphanous autoregulatory) domain.

Contains 1 FH2 (formin homology 2) domain.

Contains 1 GBD/FH3 (Rho GTPase-binding/formin homology 3) domain.

Sequence caution

The sequence AAH21906.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA07870.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SRGAP2O750443EBI-720020,EBI-1051034

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95466-1)

Also known as: FMNL1alpha;

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.
Isoform 2 (identifier: O95466-2)

Also known as: FMNL1beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1071-1100: VIKTVPFTARTGKRTSRLLCEASLGEEMPL → DLRNQPYIRADTGRRSARRRPPGPPLQVTSDLSL
Isoform 3 (identifier: O95466-3)

Also known as: FMNL1gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     1070-1070: T → TGKGLARPWSYPQSVLLCFLLTQCAILWGTGCHTASCYLFCFSFLFPFSTPLHLPHPHS
Note: Due to intron retention. Constitutively activated form, probably due to alterations in the DAD domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 11001099Formin-like protein 1
PRO_0000194890

Regions

Domain27 – 468442GBD/FH3
Domain632 – 1023392FH2
Domain1059 – 109032DAD
Compositional bias459 – 616158Pro-rich

Amino acid modifications

Modified residue71Phosphoserine Ref.11
Modified residue1841Phosphoserine Ref.9 Ref.11 Ref.12
Modified residue6241Phosphoserine Ref.8 Ref.9 Ref.11 Ref.12
Lipidation21N-myristoyl glycine Ref.7

Natural variations

Alternative sequence10701T → TGKGLARPWSYPQSVLLCFL LTQCAILWGTGCHTASCYLF CFSFLFPFSTPLHLPHPHS in isoform 3.
VSP_043845
Alternative sequence1071 – 110030VIKTV…EEMPL → DLRNQPYIRADTGRRSARRR PPGPPLQVTSDLSL in isoform 2.
VSP_013977

Experimental info

Sequence conflict4551P → A in AAP32476. Ref.1
Sequence conflict4551P → A in AAL99920. Ref.3
Sequence conflict4551P → A in AAH73988. Ref.4
Sequence conflict6021Missing in AAH21906. Ref.4
Sequence conflict6291G → R in CAA07870. Ref.5
Isoform 2:
Sequence conflict1101 – 11022DL → EV in AAH21906. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FMNL1alpha) [UniParc].

Last modified June 16, 2009. Version 3.
Checksum: 91F9CE2B3B526FFC

FASTA1,100121,854
        10         20         30         40         50         60 
MGNAAGSAEQ PAGPAAPPPK QPAPPKQPMP AAGELEERFN RALNCMNLPP DKVQLLSQYD 

        70         80         90        100        110        120 
NEKKWELICD QERFQVKNPP AAYIQKLKSY VDTGGVSRKV AADWMSNLGF KRRVQESTQV 

       130        140        150        160        170        180 
LRELETSLRT NHIGWVQEFL NEENRGLDVL LEYLAFAQCS VTYDMESTDN GASNSEKNKP 

       190        200        210        220        230        240 
LEQSVEDLSK GPPSSVPKSR HLTIKLTPAH SRKALRNSRI VSQKDDVHVC IMCLRAIMNY 

       250        260        270        280        290        300 
QSGFSLVMNH PACVNEIALS LNNKNPRTKA LVLELLAAVC LVRGGHDIIL AAFDNFKEVC 

       310        320        330        340        350        360 
GEQHRFEKLM EYFRNEDSNI DFMVACMQFI NIVVHSVENM NFRVFLQYEF THLGLDLYLE 

       370        380        390        400        410        420 
RLRLTESDKL QVQIQAYLDN IFDVGALLED TETKNAVLEH MEELQEQVAL LTERLRDAEN 

       430        440        450        460        470        480 
ESMAKIAELE KQLSQARKEL ETLRERFSES TAMGPSRRPP EPEKAPPAAP TRPSALELKV 

       490        500        510        520        530        540 
EELEEKGLIR ILRGPGDAVS IEILPVAVAT PSGGDAPTPG VPTGSPSPDL APAAEPAPGA 

       550        560        570        580        590        600 
APPPPPPLPG LPSPQEAPPS APPQAPPLPG SPEPPPAPPL PGDLPPPPPP PPPPPGTDGP 

       610        620        630        640        650        660 
VPPPPPPPPP PPGGPPDALG RRDSELGPGV KAKKPIQTKF RMPLLNWVAL KPSQITGTVF 

       670        680        690        700        710        720 
TELNDEKVLQ ELDMSDFEEQ FKTKSQGPSL DLSALKSKAA QKAPSKATLI EANRAKNLAI 

       730        740        750        760        770        780 
TLRKGNLGAE RICQAIEAYD LQALGLDFLE LLMRFLPTEY ERSLITRFER EQRPMEELSE 

       790        800        810        820        830        840 
EDRFMLCFSR IPRLPERMTT LTFLGNFPDT AQLLMPQLNA IIAASMSIKS SDKLRQILEI 

       850        860        870        880        890        900 
VLAFGNYMNS SKRGAAYGFR LQSLDALLEM KSTDRKQTLL HYLVKVIAEK YPQLTGFHSD 

       910        920        930        940        950        960 
LHFLDKAGSV SLDSVLADVR SLQRGLELTQ REFVRQDDCM VLKEFLRANS PTMDKLLADS 

       970        980        990       1000       1010       1020 
KTAQEAFESV VEYFGENPKT TSPGLFFSLF SRFIKAYKKA EQEVEQWKKE AAAQEAGADT 

      1030       1040       1050       1060       1070       1080 
PGKGEPPAPK SPPKARRPQM DLISELKRRQ QKEPLIYESD RDGAIEDIIT VIKTVPFTAR 

      1090       1100 
TGKRTSRLLC EASLGEEMPL 

« Hide

Isoform 2 (FMNL1beta) [UniParc].

Checksum: 74CFC7C3D5ABCC23
Show »

FASTA1,104122,409
Isoform 3 (FMNL1gamma) [UniParc].

Checksum: 43D0BA60ABEA6AD5
Show »

FASTA1,158128,335

References

« Hide 'large scale' references
[1]"Human leukocyte formin: a new protein preferentially expressed in lymphocytes."
Favaro P.M.B., Medina S.S., Basseres D.S., Costa F.F., Saad S.T.O.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Bone marrow.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Identification of novel tumor antigens in CLL by SEREX: assessment of their potential as targets for immunotherapeutic approaches."
Krackhardt A.M., Witzens M., Harig S., Hodi F.S., Zauls A.J., Chessia M., Barrett P., Gribben J.G.
Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 110-1100 (ISOFORM 1).
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 419-1100 (ISOFORMS 1 AND 2).
Tissue: Brain and Lymph.
[5]"The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal dementia and parkinsonism linked to chromosome 17."
Aronsson F.C., Magnusson P., Andersson B., Karsten S.L., Shibasaki Y., Lendon C.L., Goate A.M., Brookes A.J.
Hum. Genet. 103:340-345(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 629-1100 (ISOFORM 2).
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 642-1100 (ISOFORM 2).
[7]"Formin-like 1 (FMNL1) is regulated by N-terminal myristoylation and induces polarized membrane blebbing."
Han Y., Eppinger E., Schuster I.G., Weigand L.U., Liang X., Kremmer E., Peschel C., Krackhardt A.M.
J. Biol. Chem. 284:33409-33417(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 668-1100 (ISOFORM 3), MYRISTOYLATION AT GLY-2, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-624, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment."
Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.
J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184 AND SER-624, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: T-cell.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-184 AND SER-624, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184 AND SER-624, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Identification and characterization of a set of conserved and new regulators of cytoskeletal organisation, cell morphology and migration."
Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V., Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.
BMC Biol. 9:54-54(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Bi-modal regulation of a formin by srGAP2."
Mason F.M., Heimsath E.G., Higgs H.N., Soderling S.H.
J. Biol. Chem. 286:6577-6586(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRGAP2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY278319 mRNA. Translation: AAP32476.1.
AC008105 mRNA. No translation available.
AF432213 mRNA. Translation: AAL99920.1.
BC001710 mRNA. Translation: AAH01710.2.
BC009000 mRNA. Translation: AAH09000.2.
BC021906 mRNA. Translation: AAH21906.1. Different initiation.
BC073988 mRNA. Translation: AAH73988.1.
AJ008112 mRNA. Translation: CAA07870.1. Different initiation.
CR456759 mRNA. Translation: CAG33040.1.
FJ534522 mRNA. Translation: ACR19333.1.
RefSeqNP_005883.2. NM_005892.3.
UniGeneHs.100217.

3D structure databases

ProteinModelPortalO95466.
SMRO95466. Positions 117-421, 633-1074.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107208. 63 interactions.
IntActO95466. 5 interactions.
MINTMINT-1188250.
STRING9606.ENSP00000329219.

PTM databases

PhosphoSiteO95466.

Proteomic databases

PaxDbO95466.
PRIDEO95466.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328118; ENSP00000327442; ENSG00000184922. [O95466-2]
ENST00000331495; ENSP00000329219; ENSG00000184922. [O95466-1]
GeneID752.
KEGGhsa:752.
UCSCuc002iin.3. human. [O95466-1]
uc002iiq.3. human. [O95466-2]

Organism-specific databases

CTD752.
GeneCardsGC17P043299.
HGNCHGNC:1212. FMNL1.
HPAHPA008129.
HPA028288.
MIM604656. gene.
neXtProtNX_O95466.
PharmGKBPA28186.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149898.
HOVERGENHBG053118.
OMAKSYLDTG.
OrthoDBEOG7F7W8J.
PhylomeDBO95466.
TreeFamTF325155.

Gene expression databases

ArrayExpressO95466.
BgeeO95466.
CleanExHS_FMNL1.
GenevestigatorO95466.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR014767. Diaphanous_autoregulatory.
IPR015425. FH2_Formin.
IPR010472. FH3_dom.
IPR027657. FMNL1.
IPR010473. GTPase-bd.
IPR014768. GTPase-bd/formin_homology_3.
[Graphical view]
PANTHERPTHR23213:SF27. PTHR23213:SF27. 1 hit.
PfamPF06367. Drf_FH3. 1 hit.
PF06371. Drf_GBD. 2 hits.
PF02181. FH2. 1 hit.
[Graphical view]
SMARTSM00498. FH2. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 2 hits.
PROSITEPS51231. DAD. 1 hit.
PS51444. FH2. 1 hit.
PS51232. GBD_FH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFMNL1.
GenomeRNAi752.
NextBio3034.
PROO95466.
SOURCESearch...

Entry information

Entry nameFMNL_HUMAN
AccessionPrimary (citable) accession number: O95466
Secondary accession number(s): D2DGW2 expand/collapse secondary AC list , Q6DKG5, Q6IBP3, Q86UH1, Q8N671, Q8TDH1, Q96H10
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: June 16, 2009
Last modified: March 19, 2014
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM