Q9NZ56 (FMN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Formin-2

Gene names

Name:

FMN2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1722 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis By similarity. Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization. Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2. Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest. Protects cells against apoptosis by protecting CDKN1A against degradation. Ref.5 Ref.6
Subunit structure	Interacts with SPIRE1. Binds actin. Interacts with CDKN1A. Ref.4 Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm › cytoskeleton. Cytoplasm › perinuclear region. Cytoplasm › cytosol. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasm › cell cortex By similarity. Nucleus › nucleolus. Note: Recruited to the membranes via its interaction with SPIRE1. Colocalizes with the actin cytoskeleton. Detected at the cleavage furrow during asymmetric oocyte division and polar body extrusion By similarity. Ref.4 Ref.6
Tissue specificity	Expressed almost exclusively in the developing and mature central nervous system. Ref.3
Induction	Up-regulated in response to cellular stress, hypoxia and DNA damage via NF-kappa-B. Ref.6
Sequence similarities	Belongs to the formin homology family. Cappuccino subfamily. Contains 1 FH1 (formin homology 1) domain. Contains 1 FH2 (formin homology 2) domain.
Sequence caution	The sequence AAF72884.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.

Ontologies

Keywords
Biological process	DNA damage Protein transport Stress response Transport
Cellular component	Cell membrane Cytoplasm Cytoplasmic vesicle Cytoskeleton Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	Actin-binding
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from mutant phenotype Ref.6. Source: UniProtKB cellular response to hypoxia Inferred from mutant phenotype Ref.6. Source: UniProtKB establishment of meiotic spindle localization Inferred from sequence or structural similarity. Source: BHF-UCL formin-nucleated actin cable assembly Inferred from sequence or structural similarity. Source: UniProtKB intracellular signal transduction Inferred from electronic annotation. Source: InterPro intracellular transport Inferred from sequence or structural similarity. Source: UniProtKB meiotic chromosome movement towards spindle pole Inferred from sequence or structural similarity. Source: BHF-UCL meiotic metaphase I Inferred from sequence or structural similarity. Source: BHF-UCL multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of protein catabolic process Inferred from mutant phenotype Ref.6. Source: UniProtKB oogenesis Inferred from sequence or structural similarity. Source: BHF-UCL polar body extrusion after meiotic divisions Inferred from sequence or structural similarity. Source: BHF-UCL protein transport Inferred from electronic annotation. Source: UniProtKB-KW response to DNA damage stimulus Inferred from mutant phenotype Ref.6. Source: UniProtKB vesicle-mediated transport Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell cortex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasmic vesicle membrane Inferred from sequence or structural similarity. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay Ref.4. Source: UniProtKB nucleolus Inferred from direct assay Ref.6. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	actin binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1722

1722

Formin-2

PRO_0000194888

Regions

Domain

758 – 1268

511

FH1

Domain

1283 – 1698

416

FH2

Region

1715 – 1722

8

Important for interaction with SPIRE1

Coiled coil

193 – 231

39

Potential

Coiled coil

670 – 706

37

Potential

Coiled coil

1567 – 1597

31

Potential

Coiled coil

1677 – 1699

23

Potential

Compositional bias

200 – 227

28

Gln-rich

Compositional bias

758 – 1268

511

Pro-rich

Amino acid modifications

Modified residue

361

1

Phosphoserine By similarity

Modified residue

516

1

Phosphoserine By similarity

Modified residue

746

1

Phosphothreonine By similarity

Modified residue

747

1

Phosphoserine By similarity

Natural variations

Natural variant

1148

1

R → G. Ref.2
Corresponds to variant rs12732924 [ dbSNP | Ensembl ].

VAR_059290

Natural variant

1291

1

R → G.
Corresponds to variant rs12732924 [ dbSNP | Ensembl ].

VAR_049094

Natural variant

1468

1

R → H. Ref.2
Corresponds to variant rs3795677 [ dbSNP | Ensembl ].

VAR_033932

Experimental info

Mutagenesis

1715

1

K → A or E: Abolishes interaction with SPIRE1. Ref.8

Mutagenesis

1717

1

K → A: Strongly reduces interaction with SPIRE1. Ref.8

Mutagenesis

1721

1

K → A or E: Strongly reduces interaction with SPIRE1. Ref.8

Sequence conflict

644

1

E → EDDGE in BAD92390. Ref.2

Sequence conflict

768

1

P → T in BAD92390. Ref.2

Sequence conflict

1426 – 1427

2

EN → TR in AAF72885. Ref.3

Secondary structure

1

.

.

.

.

.

1722

Helix Strand Turn

Details...

Beta strand

1706 – 1708

3

Helix

1714 – 1719

6

Sequences

	Sequence		Length	Mass (Da)
	Q9NZ56 [UniParc]. Last modified January 15, 2008. Version 4. Checksum: 26525AC7868A949C	FASTA	1,722	180,106
	10 20 30 40 50 60 MGNQDGKLKR SAGDALHEGG GGAEDALGPR DVEATKKGSG GKKALGKHGK GGGGGGGGGE 70 80 90 100 110 120 SGKKKSKSDS RASVFSNLRI RKNLSKGKGA GGSREDVLDS QALQTGELDS AHSLLTKTPD 130 140 150 160 170 180 LSLSADEAGL SDTECADPFE VTGPGGPGPA EARVGGRPIA EDVETAAGAQ DGQRTSSGSD 190 200 210 220 230 240 TDIYSFHSAT EQEDLLSDIQ QAIRLQQQQQ QQLQLQLQQQ QQQQQLQGAE EPAAPPTAVS 250 260 270 280 290 300 PQPGAFLGLD RFLLGPSGGA GEAPGSPDTE QALSALSDLP ESLAAEPREP QQPPSPGGLP 310 320 330 340 350 360 VSEAPSLPAA QPAAKDSPSS TAFPFPEAGP GEEAAGAPVR GAGDTDEEGE EDAFEDAPRG 370 380 390 400 410 420 SPGEEWAPEV GEDAPQRLGE EPEEEAQGPD APAAASLPGS PAPSQRCFKP YPLITPCYIK 430 440 450 460 470 480 TTTRQLSSPN HSPSQSPNQS PRIKRRPEPS LSRGSRTALA SVAAPAKKHR ADGGLAAGLS 490 500 510 520 530 540 RSADWTEELG ARTPRVGGSA HLLERGVASD SGGGVSPALA AKASGAPAAA DGFQNVFTGR 550 560 570 580 590 600 TLLEKLFSQQ ENGPPEEAEK FCSRIIAMGL LLPFSDCFRE PCNQNAQTNA ASFDQDQLYT 610 620 630 640 650 660 WAAVSQPTHS LDYSEGQFPR RVPSMGPPSK PPDEEHRLED AETESQSAVS ETPQKRSDAV 670 680 690 700 710 720 QKEVVDMKSE GQATVIQQLE QTIEDLRTKI AELERQYPAL DTEVASGHQG LENGVTASGD 730 740 750 760 770 780 VCLEALRLEE KEVRHHRILE AKSIQTSPTE EGGVLTLPPV DGLPGRPPCP PGAESGPQTK 790 800 810 820 830 840 FCSEISLIVS PRRISVQLDS HQPTQSISQP PPPPSLLWSA GQGQPGSQPP HSISTEFQTS 850 860 870 880 890 900 HEHSVSSAFK NSCNIPSPPP LPCTESSSSM PGLGMVPPPP PPLPGMTVPT LPSTAIPQPP 910 920 930 940 950 960 PLQGTEMLPP PPPPLPGAGI PPPPPLPGAG ILPLPPLPGA GIPPPPPLPG AAIPPPPPLP 970 980 990 1000 1010 1020 GAGIPLPPPL PGAGIPPPPP LPGAGIPPPP PLPGAGIPPP PPLPGAGIPP PPPLPGAGIP 1030 1040 1050 1060 1070 1080 PPPPLPGAGI PPPPPLPGAG IPPPPPLPGA GIPPPPPLPG AGIPPPPPLP GAGIPPPPPL 1090 1100 1110 1120 1130 1140 PGAGIPPPPP LPGAGIPPPP PLPGVGIPPP PPLPGAGIPP PPPLPGAGIP PPPPLPGAGI 1150 1160 1170 1180 1190 1200 PPPPPLPRVG IPPPPPLPGA GIPPPPPLPG AGIPPPPPLP GVGIPPPPPL PGVGIPPPPP 1210 1220 1230 1240 1250 1260 LPGAGIPPPP PLPGMGIPPA PAPPLPPPGT GIPPPPLLPV SGPPLLPQVG SSTLPTPQVC 1270 1280 1290 1300 1310 1320 GFLPPPLPSG LFGLGMNQDK GSRKQPIEPC RPMKPLYWTR IQLHSKRDSS TSLIWEKIEE 1330 1340 1350 1360 1370 1380 PSIDCHEFEE LFSKTAVKER KKPISDTISK TKAKQVVKLL SNKRSQAVGI LMSSLHLDMK 1390 1400 1410 1420 1430 1440 DIQHAVVNLD NSVVDLETLQ ALYENRAQSD ELEKIEKHGR SSKDKENAKS LDKPEQFLYE 1450 1460 1470 1480 1490 1500 LSLIPNFSER VFCILFQSTF SESICSIRRK LELLQKLCET LKNGPGVMQV LGLVLAFGNY 1510 1520 1530 1540 1550 1560 MNGGNKTRGQ ADGFGLDILP KLKDVKSSDN SRSLLSYIVS YYLRNFDEDA GKEQCLFPLP 1570 1580 1590 1600 1610 1620 EPQDLFQASQ MKFEDFQKDL RKLKKDLKAC EVEAGKVYQV SSKEHMQPFK ENMEQFIIQA 1630 1640 1650 1660 1670 1680 KIDQEAEENS LTETHKCFLE TTAYFFMKPK LGEKEVSPNA FFSIWHEFSS DFKDFWKKEN 1690 1700 1710 1720 KLLLQERVKE AEEVCRQKKG KSLYKIKPRH DSGIKAKISM KT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 395-1722, VARIANTS GLY-1148 AND HIS-1468. Tissue: Brain.
[3]	"Formin-2, a novel formin homology protein of the cappuccino subfamily, is highly expressed in the developing and adult central nervous system." Leader B., Leder P. Mech. Dev. 93:221-231(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 396-727 AND 1426-1722, TISSUE SPECIFICITY. Tissue: Brain.
[4]	"Effects of genistein on beta-catenin signaling and subcellular distribution of actin-binding proteins in human umbilical CD105-positive stromal cells." Shieh D.B., Li R.Y., Liao J.M., Chen G.D., Liou Y.M. J. Cell. Physiol. 223:423-434(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACTIN, SUBCELLULAR LOCATION.
[5]	"Differential role of actin-binding proteins in controlling the adipogenic differentiation of human CD105-positive Wharton's Jelly cells." Peng K.W., Liou Y.M. Biochim. Biophys. Acta 1820:469-481(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Identification and functional characterization of FMN2, a regulator of the cyclin-dependent kinase inhibitor p21." Yamada K., Ono M., Perkins N.D., Rocha S., Lamond A.I. Mol. Cell 49:922-933(2013) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDKN1A, SUBCELLULAR LOCATION, INDUCTION, MASS SPECTROMETRY.
[7]	"Molecular basis of actin nucleation factor cooperativity: crystal structure of the Spir-1 kinase non-catalytic C-lobe domain (KIND)*formin-2 formin SPIR interaction motif (FSI) complex." Zeth K., Pechlivanis M., Samol A., Pleiser S., Vonrhein C., Kerkhoff E. J. Biol. Chem. 286:30732-30739(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1694-1722 IN COMPLEX WITH SPIRE1, INTERACTION WITH SPIRE1.
[8]	"Structure and function of the interacting domains of Spire and Fmn-family formins." Vizcarra C.L., Kreutz B., Rodal A.A., Toms A.V., Lu J., Zheng W., Quinlan M.E., Eck M.J. Proc. Natl. Acad. Sci. U.S.A. 108:11884-11889(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1701-1722 IN COMPLEX WITH SPIRE1, INTERACTION WITH SPIRE1, MUTAGENESIS OF LYS-1715; LYS-1717 AND LYS-1721.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AL359918 , AL513342, AL590490, AL646016 Genomic DNA. Translation: CAQ10135.1.
AL513342 , AL359918, AL590490, AL646016 Genomic DNA. Translation: CAQ10526.1.
AL590490 , AL359918, AL513342, AL646016 Genomic DNA. Translation: CAQ10976.1.
AL646016 , AL359918, AL513342, AL590490 Genomic DNA. Translation: CAQ08405.1.
AB209153 mRNA. Translation: BAD92390.1.
AF218941 mRNA. Translation: AAF72884.1. Sequence problems.
AF218942 mRNA. Translation: AAF72885.1.

IPI

IPI00936831.

RefSeq

NP_064450.3. NM_020066.4.

UniGene

Hs.24889.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YLE	X-ray	1.80	B	1694-1722	[»]
3R7G	X-ray	2.20	B	1701-1722	[»]

ProteinModelPortal

Q9NZ56.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000318884.

PTM databases

PhosphoSite

Q9NZ56.

Polymorphism databases

DMDM

166215083.

Proteomic databases

PaxDb

Q9NZ56.

PRIDE

Q9NZ56.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319653; ENSP00000318884; ENSG00000155816.

GeneID

56776.

KEGG

hsa:56776.

UCSC

uc010pyd.2. human.

Organism-specific databases

CTD

56776.

GeneCards

GC01P240177.

H-InvDB

HIX0021237.

HGNC

HGNC:14074. FMN2.

HPA

HPA004937.

MIM

606373. gene.

neXtProt

NX_Q9NZ56.

PharmGKB

PA28185.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG264408.

HOGENOM

HOG000112618.

HOVERGEN

HBG107923.

InParanoid

Q9NZ56.

KO

K02184.

OMA

EHRPKDA.

OrthoDB

EOG4M0F16.

Gene expression databases

ArrayExpress

Q9NZ56.

Bgee

Q9NZ56.

CleanEx

HS_FMN2.

Genevestigator

Q9NZ56.

Family and domain databases

InterPro

IPR003104. Actin-bd_FH2/DRF_autoreg.
IPR000591. DEP_dom.
IPR015425. FH2_actin-bd.
IPR009408. Formin_homology_1.
[Graphical view]

Pfam

PF06346. Drf_FH1. 4 hits.
PF02181. FH2. 1 hit.
[Graphical view]

SMART

SM00498. FH2. 1 hit.
[Graphical view]

SUPFAM

SSF101447. FH2_actin_bd. 1 hit.

PROSITE

PS51444. FH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

56776.

NextBio

62219.

SOURCE

Search...

Entry information

Entry name

FMN2_HUMAN

Accession

Primary (citable) accession number: Q9NZ56
Secondary accession number(s): B0QZA7 , Q59GF6, Q5VU37, Q9NZ55

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	January 15, 2008
Last modified:	May 1, 2013
This is version 101 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.