FMNL2_HUMAN
ID FMNL2_HUMAN Reviewed; 1086 AA.
AC Q96PY5; B2RZH5; Q14CC9; Q4ZG52; Q8N3E0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Formin-like protein 2;
DE AltName: Full=Formin homology 2 domain-containing protein 2;
GN Name=FMNL2; Synonyms=FHOD2, KIAA1902;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 85-1086 (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP IDENTIFICATION (ISOFORMS 1 AND 2).
RX PubMed=12684686;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human FMNL1, FMNL2 and FMNL3 genes
RT in silico.";
RL Int. J. Oncol. 22:1161-1168(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [8]
RP FUNCTION.
RX PubMed=21834987; DOI=10.1186/1741-7007-9-54;
RA Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V.,
RA Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.;
RT "Identification and characterization of a set of conserved and new
RT regulators of cytoskeletal organisation, cell morphology and migration.";
RL BMC Biol. 9:54-54(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Plays a role in the regulation of cell morphology and
CC cytoskeletal organization. Required in the cortical actin filament
CC dynamics. {ECO:0000269|PubMed:21834987}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96PY5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96PY5-3; Sequence=VSP_025887;
CC -!- DOMAIN: The DAD domain regulates activation via by an autoinhibitory
CC interaction with the GBD/FH3 domain. This autoinhibition is released
CC upon competitive binding of an activated GTPase. The release of DAD
CC allows the FH2 domain to then nucleate and elongate nonbranched actin
CC filaments (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the formin homology family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI13879.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=AAI14439.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=AAX88959.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAB67795.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB067489; BAB67795.1; ALT_INIT; mRNA.
DR EMBL; AC012066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012443; AAX88959.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC093794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113878; AAI13879.1; ALT_SEQ; mRNA.
DR EMBL; BC114438; AAI14439.1; ALT_SEQ; mRNA.
DR EMBL; BC167159; AAI67159.1; -; mRNA.
DR EMBL; AL834396; CAD39058.1; -; mRNA.
DR CCDS; CCDS46429.1; -. [Q96PY5-3]
DR RefSeq; NP_443137.2; NM_052905.3. [Q96PY5-3]
DR PDB; 4YC7; X-ray; 2.50 A; B=1-379.
DR PDBsum; 4YC7; -.
DR AlphaFoldDB; Q96PY5; -.
DR SMR; Q96PY5; -.
DR BioGRID; 125355; 58.
DR ELM; Q96PY5; -.
DR IntAct; Q96PY5; 13.
DR MINT; Q96PY5; -.
DR STRING; 9606.ENSP00000288670; -.
DR iPTMnet; Q96PY5; -.
DR PhosphoSitePlus; Q96PY5; -.
DR BioMuta; FMNL2; -.
DR DMDM; 238054383; -.
DR EPD; Q96PY5; -.
DR jPOST; Q96PY5; -.
DR MassIVE; Q96PY5; -.
DR MaxQB; Q96PY5; -.
DR PaxDb; Q96PY5; -.
DR PeptideAtlas; Q96PY5; -.
DR PRIDE; Q96PY5; -.
DR ProteomicsDB; 77786; -. [Q96PY5-1]
DR ProteomicsDB; 77787; -. [Q96PY5-3]
DR Antibodypedia; 10309; 103 antibodies from 24 providers.
DR DNASU; 114793; -.
DR Ensembl; ENST00000288670.14; ENSP00000288670.9; ENSG00000157827.20. [Q96PY5-3]
DR GeneID; 114793; -.
DR KEGG; hsa:114793; -.
DR MANE-Select; ENST00000288670.14; ENSP00000288670.9; NM_052905.4; NP_443137.2. [Q96PY5-3]
DR UCSC; uc002tye.3; human. [Q96PY5-1]
DR CTD; 114793; -.
DR DisGeNET; 114793; -.
DR GeneCards; FMNL2; -.
DR HGNC; HGNC:18267; FMNL2.
DR HPA; ENSG00000157827; Tissue enhanced (brain).
DR MIM; 616285; gene.
DR neXtProt; NX_Q96PY5; -.
DR OpenTargets; ENSG00000157827; -.
DR PharmGKB; PA28144; -.
DR VEuPathDB; HostDB:ENSG00000157827; -.
DR eggNOG; KOG1923; Eukaryota.
DR GeneTree; ENSGT00940000155515; -.
DR HOGENOM; CLU_003597_0_0_1; -.
DR InParanoid; Q96PY5; -.
DR OMA; MMPGFSP; -.
DR OrthoDB; 288325at2759; -.
DR PhylomeDB; Q96PY5; -.
DR TreeFam; TF325155; -.
DR PathwayCommons; Q96PY5; -.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR SignaLink; Q96PY5; -.
DR BioGRID-ORCS; 114793; 26 hits in 1074 CRISPR screens.
DR ChiTaRS; FMNL2; human.
DR GeneWiki; FMNL2; -.
DR GenomeRNAi; 114793; -.
DR Pharos; Q96PY5; Tbio.
DR PRO; PR:Q96PY5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96PY5; protein.
DR Bgee; ENSG00000157827; Expressed in inferior vagus X ganglion and 186 other tissues.
DR ExpressionAtlas; Q96PY5; baseline and differential.
DR Genevisible; Q96PY5; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR DisProt; DP02609; -.
DR Gene3D; 1.20.58.2220; -; 1.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014767; DAD_dom.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR InterPro; IPR010472; FH3_dom.
DR InterPro; IPR027656; FMNL2.
DR InterPro; IPR043592; FMNL_animal.
DR InterPro; IPR014768; GBD/FH3_dom.
DR InterPro; IPR010473; GTPase-bd.
DR PANTHER; PTHR45857; PTHR45857; 1.
DR PANTHER; PTHR45857:SF5; PTHR45857:SF5; 1.
DR Pfam; PF06367; Drf_FH3; 1.
DR Pfam; PF06371; Drf_GBD; 2.
DR Pfam; PF02181; FH2; 1.
DR SMART; SM01139; Drf_FH3; 1.
DR SMART; SM01140; Drf_GBD; 1.
DR SMART; SM00498; FH2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51231; DAD; 1.
DR PROSITE; PS51444; FH2; 1.
DR PROSITE; PS51232; GBD_FH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Lipoprotein; Myristate;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..1086
FT /note="Formin-like protein 2"
FT /id="PRO_0000289093"
FT DOMAIN 23..469
FT /note="GBD/FH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00579"
FT DOMAIN 616..1007
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT DOMAIN 1040..1079
FT /note="DAD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00577"
FT REGION 513..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..538
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..597
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:20213681"
FT VAR_SEQ 1057..1086
FT /note="VLKTVPFTARTAKRGSRFFCEPVLTEEYHY -> DLRNQPYRRADAVRRSVR
FT RRFDDQNLRSVNGAEITM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11572484,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_025887"
FT VARIANT 352
FT /note="Y -> C (in dbSNP:rs34119671)"
FT /id="VAR_032570"
FT VARIANT 504
FT /note="M -> T (in dbSNP:rs11897929)"
FT /id="VAR_032571"
FT CONFLICT 570
FT /note="P -> PP (in Ref. 1; BAB67795, 3; AAI67159 and 4;
FT CAD39058)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="A -> S (in Ref. 1; BAB67795 and 3; AAI67159)"
FT /evidence="ECO:0000305"
FT CONFLICT 964
FT /note="T -> R (in Ref. 4; CAD39058)"
FT /evidence="ECO:0000305"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 46..53
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 57..69
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 76..87
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 103..116
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 119..126
FT /evidence="ECO:0007829|PDB:4YC7"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 132..145
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 206..216
FT /evidence="ECO:0007829|PDB:4YC7"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 220..232
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 235..243
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 247..253
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 260..275
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 279..294
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 301..309
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 314..329
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 334..346
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 349..356
FT /evidence="ECO:0007829|PDB:4YC7"
FT HELIX 362..374
FT /evidence="ECO:0007829|PDB:4YC7"
SQ SEQUENCE 1086 AA; 123321 MW; 951ED0A26232F640 CRC64;
MGNAGSMDSQ QTDFRAHNVP LKLPMPEPGE LEERFAIVLN AMNLPPDKAR LLRQYDNEKK
WELICDQERF QVKNPPHTYI QKLKGYLDPA VTRKKFRRRV QESTQVLREL EISLRTNHIG
WVREFLNEEN KGLDVLVEYL SFAQYAVTFD FESVESTVES SVDKSKPWSR SIEDLHRGSN
LPSPVGNSVS RSGRHSALRY NTLPSRRTLK NSRLVSKKDD VHVCIMCLRA IMNYQYGFNM
VMSHPHAVNE IALSLNNKNP RTKALVLELL AAVCLVRGGH EIILSAFDNF KEVCGEKQRF
EKLMEHFRNE DNNIDFMVAS MQFINIVVHS VEDMNFRVHL QYEFTKLGLD EYLDKLKHTE
SDKLQVQIQA YLDNVFDVGA LLEDAETKNA ALERVEELEE NISHLSEKLQ DTENEAMSKI
VELEKQLMQR NKELDVVREI YKDANTQVHT LRKMVKEKEE AIQRQSTLEK KIHELEKQGT
IKIQKKGDGD IAILPVVASG TLSMGSEVVA GNSVGPTMGA ASSGPLPPPP PPLPPSSDTP
ETVQNGPVTP PMPPPPPPPP PPPPPPPPPP PPPLPGPAAE TVPAPPLAPP LPSAPPLPGT
SSPTVVFNSG LAAVKIKKPI KTKFRMPVFN WVALKPNQIN GTVFNEIDDE RILEDLNVDE
FEEIFKTKAQ GPAIDLSSSK QKIPQKGSNK VTLLEANRAK NLAITLRKAG KTADEICKAI
HVFDLKTLPV DFVECLMRFL PTENEVKVLR LYERERKPLE NLSDEDRFMM QFSKIERLMQ
KMTIMAFIGN FAESIQMLTP QLHAIIAASV SIKSSQKLKK ILEIILALGN YMNSSKRGAV
YGFKLQSLDL LLDTKSTDRK QTLLHYISNV VKEKYHQVSL FYNELHYVEK AAAVSLENVL
LDVKELQRGM DLTKREYTMH DHNTLLKEFI LNNEGKLKKL QDDAKIAQDA FDDVVKYFGE
NPKTTPPSVF FPVFVRFVKA YKQAEEENEL RKKQEQALME KLLEQEALME QQDPKSPSHK
SKRQQQELIA ELRRRQVKDN RHVYEGKDGA IEDIITVLKT VPFTARTAKR GSRFFCEPVL
TEEYHY
