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Protein

Formin-like protein 1

Gene

FMNL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • actin filament severing Source: UniProtKB
  • cortical actin cytoskeleton organization Source: UniProtKB
  • regulation of cell shape Source: UniProtKB
  • substrate-dependent cell migration Source: Ensembl

Enzyme and pathway databases

ReactomeiR-HSA-5663220. RHO GTPases Activate Formins.

Names & Taxonomyi

Protein namesi
Recommended name:
Formin-like protein 1
Alternative name(s):
CLL-associated antigen KW-13
Leukocyte formin
Gene namesi
Name:FMNL1
Synonyms:C17orf1, C17orf1B, FMNL, FRL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000184922.13.
HGNCiHGNC:1212. FMNL1.

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 membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi752.
OpenTargetsiENSG00000184922.
PharmGKBiPA28186.

Polymorphism and mutation databases

BioMutaiFMNL1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001948902 – 1100Formin-like protein 1Add BLAST1099

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1
Modified residuei7PhosphoserineCombined sources1
Modified residuei184PhosphoserineCombined sources1
Modified residuei624PhosphoserineCombined sources1
Modified residuei693PhosphoserineCombined sources1
Modified residuei1031PhosphoserineCombined sources1

Post-translational modificationi

Myristoylation mediates membrane localization and blebbing.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiO95466.
PaxDbiO95466.
PeptideAtlasiO95466.
PRIDEiO95466.

PTM databases

iPTMnetiO95466.
PhosphoSitePlusiO95466.
SwissPalmiO95466.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000184922.
CleanExiHS_FMNL1.
ExpressionAtlasiO95466. baseline and differential.
GenevisibleiO95466. HS.

Organism-specific databases

HPAiHPA008129.
HPA028288.

Interactioni

Subunit structurei

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.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107208. 73 interactors.
IntActiO95466. 16 interactors.
MINTiMINT-1188250.
STRINGi9606.ENSP00000329219.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YDHX-ray3.80A/C1-458[»]
ProteinModelPortaliO95466.
SMRiO95466.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 468GBD/FH3PROSITE-ProRule annotationAdd BLAST442
Domaini632 – 1023FH2PROSITE-ProRule annotationAdd BLAST392
Domaini1059 – 1090DADPROSITE-ProRule annotationAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi459 – 616Pro-richAdd BLAST158

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the formin homology family.Curated

Phylogenomic databases

eggNOGiKOG1923. Eukaryota.
ENOG410Y3DT. LUCA.
GeneTreeiENSGT00760000118986.
HOVERGENiHBG053118.
InParanoidiO95466.
OMAiPYIRADT.
OrthoDBiEOG091G01GP.
PhylomeDBiO95466.
TreeFamiTF325155.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
InterProiView protein in InterPro
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR014767. DAD_dom.
IPR015425. FH2_Formin.
IPR010472. FH3_dom.
IPR027657. FMNL1.
IPR014768. GBD/FH3_dom.
IPR010473. GTPase-bd.
PANTHERiPTHR23213:SF272. PTHR23213:SF272. 1 hit.
PfamiView protein in Pfam
PF06367. Drf_FH3. 1 hit.
PF06371. Drf_GBD. 2 hits.
PF02181. FH2. 1 hit.
SMARTiView protein in SMART
SM01139. Drf_FH3. 1 hit.
SM01140. Drf_GBD. 1 hit.
SM00498. FH2. 1 hit.
SUPFAMiSSF48371. SSF48371. 2 hits.
PROSITEiView protein in PROSITE
PS51231. DAD. 1 hit.
PS51444. FH2. 1 hit.
PS51232. GBD_FH3. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: O95466-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGNAAGSAEQ PAGPAAPPPK QPAPPKQPMP AAGELEERFN RALNCMNLPP
60 70 80 90 100
DKVQLLSQYD NEKKWELICD QERFQVKNPP AAYIQKLKSY VDTGGVSRKV
110 120 130 140 150
AADWMSNLGF KRRVQESTQV LRELETSLRT NHIGWVQEFL NEENRGLDVL
160 170 180 190 200
LEYLAFAQCS VTYDMESTDN GASNSEKNKP LEQSVEDLSK GPPSSVPKSR
210 220 230 240 250
HLTIKLTPAH SRKALRNSRI VSQKDDVHVC IMCLRAIMNY QSGFSLVMNH
260 270 280 290 300
PACVNEIALS LNNKNPRTKA LVLELLAAVC LVRGGHDIIL AAFDNFKEVC
310 320 330 340 350
GEQHRFEKLM EYFRNEDSNI DFMVACMQFI NIVVHSVENM NFRVFLQYEF
360 370 380 390 400
THLGLDLYLE RLRLTESDKL QVQIQAYLDN IFDVGALLED TETKNAVLEH
410 420 430 440 450
MEELQEQVAL LTERLRDAEN ESMAKIAELE KQLSQARKEL ETLRERFSES
460 470 480 490 500
TAMGPSRRPP EPEKAPPAAP TRPSALELKV EELEEKGLIR ILRGPGDAVS
510 520 530 540 550
IEILPVAVAT PSGGDAPTPG VPTGSPSPDL APAAEPAPGA APPPPPPLPG
560 570 580 590 600
LPSPQEAPPS APPQAPPLPG SPEPPPAPPL PGDLPPPPPP PPPPPGTDGP
610 620 630 640 650
VPPPPPPPPP PPGGPPDALG RRDSELGPGV KAKKPIQTKF RMPLLNWVAL
660 670 680 690 700
KPSQITGTVF TELNDEKVLQ ELDMSDFEEQ FKTKSQGPSL DLSALKSKAA
710 720 730 740 750
QKAPSKATLI EANRAKNLAI TLRKGNLGAE RICQAIEAYD LQALGLDFLE
760 770 780 790 800
LLMRFLPTEY ERSLITRFER EQRPMEELSE EDRFMLCFSR IPRLPERMTT
810 820 830 840 850
LTFLGNFPDT AQLLMPQLNA IIAASMSIKS SDKLRQILEI VLAFGNYMNS
860 870 880 890 900
SKRGAAYGFR LQSLDALLEM KSTDRKQTLL HYLVKVIAEK YPQLTGFHSD
910 920 930 940 950
LHFLDKAGSV SLDSVLADVR SLQRGLELTQ REFVRQDDCM VLKEFLRANS
960 970 980 990 1000
PTMDKLLADS KTAQEAFESV VEYFGENPKT TSPGLFFSLF SRFIKAYKKA
1010 1020 1030 1040 1050
EQEVEQWKKE AAAQEAGADT PGKGEPPAPK SPPKARRPQM DLISELKRRQ
1060 1070 1080 1090 1100
QKEPLIYESD RDGAIEDIIT VIKTVPFTAR TGKRTSRLLC EASLGEEMPL
Length:1,100
Mass (Da):121,854
Last modified:June 16, 2009 - v3
Checksum:i91F9CE2B3B526FFC
GO
Isoform 2 (identifier: O95466-2) [UniParc]FASTAAdd to basket
Also known as: FMNL1beta

The sequence of this isoform differs from the canonical sequence as follows:
     1071-1100: VIKTVPFTARTGKRTSRLLCEASLGEEMPL → DLRNQPYIRADTGRRSARRRPPGPPLQVTSDLSL

Show »
Length:1,104
Mass (Da):122,409
Checksum:i74CFC7C3D5ABCC23
GO
Isoform 3 (identifier: O95466-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:1,158
Mass (Da):128,335
Checksum:i43D0BA60ABEA6AD5
GO

Sequence cautioni

The sequence AAH21906 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA07870 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti455P → A in AAP32476 (Ref. 1) Curated1
Sequence conflicti455P → A in AAL99920 (Ref. 3) Curated1
Sequence conflicti455P → A in AAH73988 (PubMed:15489334).Curated1
Sequence conflicti602Missing in AAH21906 (PubMed:15489334).Curated1
Sequence conflicti629G → R in CAA07870 (PubMed:9799091).Curated1
Isoform 2 (identifier: O95466-2)
Sequence conflicti1101 – 1102DL → EV in AAH21906 (PubMed:15489334).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0438451070T → TGKGLARPWSYPQSVLLCFL LTQCAILWGTGCHTASCYLF CFSFLFPFSTPLHLPHPHS in isoform 3. 1 Publication1
Alternative sequenceiVSP_0139771071 – 1100VIKTV…EEMPL → DLRNQPYIRADTGRRSARRR PPGPPLQVTSDLSL in isoform 2. 3 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11497.1. [O95466-1]
RefSeqiNP_005883.2. NM_005892.3.
XP_006722126.1. XM_006722063.3. [O95466-3]
XP_006722133.1. XM_006722070.3. [O95466-2]
UniGeneiHs.100217.
Hs.729912.

Genome annotation databases

EnsembliENST00000331495; ENSP00000329219; ENSG00000184922. [O95466-1]
GeneIDi752.
KEGGihsa:752.
UCSCiuc002iin.4. human. [O95466-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFMNL1_HUMAN
AccessioniPrimary (citable) accession number: O95466
Secondary accession number(s): D2DGW2
, Q6DKG5, Q6IBP3, Q86UH1, Q8N671, Q8TDH1, Q96H10
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: June 16, 2009
Last modified: September 27, 2017
This is version 154 of the entry and version 3 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, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families