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O60879 (DIAP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein diaphanous homolog 2
Alternative name(s):
Diaphanous-related formin-2
Short name=DRF2
Gene names
Name:DIAPH2
Synonyms:DIA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1101 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Could be involved in oogenesis. Involved in the regulation of endosome dynamics. Implicated in a novel signal transduction pathway, in which isoform 3 and CSK are sequentially activated by RHOD to regulate the motility of early endosomes through interactions with the actin cytoskeleton. Ref.2

Subunit structure

Isoform 3 interacts with RHOD in the GTP-bound form. Ref.2

Subcellular location

Isoform 3: Cytoplasmcytosol. Early endosome. Note: Isoform 3 is cytosolic but when coexpressed with RHOD, the 2 proteins colocalize to early endosomes. Ref.2

Tissue specificity

Expressed in testis, ovary, small intestine, prostate, lung, liver, kidney and leukocytes.

Developmental stage

Expressed from E16 in ovary and testis and during P6-P16 during differentiation of ovarian follicles.

Domain

The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. 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.

Involvement in disease

Premature ovarian failure 2A (POF2A) [MIM:300511]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Belongs to the formin homology family. Diaphanous subfamily.

Contains 1 DAD (diaphanous autoregulatory) domain.

Contains 1 FH1 (formin homology 1) domain.

Contains 1 FH2 (formin homology 2) domain.

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

Ontologies

Keywords
   Biological processDifferentiation
Oogenesis
   Cellular componentCytoplasm
Endosome
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseasePremature ovarian failure
   DomainCoiled coil
Repeat
   Molecular functionDevelopmental protein
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament polymerization

Inferred from electronic annotation. Source: Ensembl

cytokinesis

Traceable author statement Ref.1. Source: ProtInc

female gamete generation

Traceable author statement Ref.1. Source: ProtInc

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

oogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

early endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionreceptor binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60879-1)

Also known as: DIA-156;

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: O60879-2)

Also known as: DIA-12C; DIA2B;

The sequence of this isoform differs from the canonical sequence as follows:
     1081-1101: DNRRVPLERSRSRHNGAISSK → VVNHPCATRANPRSAT
Isoform 3 (identifier: O60879-3)

Also known as: DIA2C;

The sequence of this isoform differs from the canonical sequence as follows:
     45-55: Missing.
     149-149: S → SIVGSKVT

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11011101Protein diaphanous homolog 2
PRO_0000194895

Regions

Domain98 – 464367GBD/FH3
Domain549 – 62375FH1
Domain628 – 1028401FH2
Domain1051 – 108131DAD
Coiled coil366 – 41853 Potential
Coiled coil487 – 54761 Potential
Coiled coil903 – 1053151 Potential
Compositional bias257 – 2604Poly-Leu
Compositional bias543 – 5464Poly-Ser
Compositional bias562 – 57211Poly-Pro
Compositional bias576 – 58510Poly-Pro
Compositional bias591 – 5977Poly-Pro
Compositional bias603 – 6086Poly-Pro
Compositional bias613 – 6164Poly-Pro
Compositional bias1038 – 10414Poly-Lys
Compositional bias1072 – 10754Arg/Lys-rich (basic)

Amino acid modifications

Modified residue11N-acetylmethionine Ref.5 Ref.7

Natural variations

Alternative sequence45 – 5511Missing in isoform 3.
VSP_012955
Alternative sequence1491S → SIVGSKVT in isoform 3.
VSP_012956
Alternative sequence1081 – 110121DNRRV…AISSK → VVNHPCATRANPRSAT in isoform 2.
VSP_001573
Natural variant4251F → L.
Corresponds to variant rs20361 [ dbSNP | Ensembl ].
VAR_049095
Natural variant4261L → V.
Corresponds to variant rs20361 [ dbSNP | Ensembl ].
VAR_049096

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (DIA-156) [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 399F1C292D79188B

FASTA1,101125,569
        10         20         30         40         50         60 
MEQPGAAASG AGGGSEEPGG GRSNKRSAGN RAANEEETKN KPKLNIQIKT LADDVRDRIT 

        70         80         90        100        110        120 
SFRKSTVKKE KPLIQHPIDS QVAMSEFPAA QPLYDERSLN LSEKEVLDLF EKMMEDMNLN 

       130        140        150        160        170        180 
EEKKAPLRNK DFTTKREMVV QYISATAKSG GLKNSKHECT LSSQEYVHEL RSGISDEKLL 

       190        200        210        220        230        240 
NCLESLRVSL TSNPVSWVNN FGHEGLGLLL DELEKLLDKK QQENIDKKNQ YKLIQCLKAF 

       250        260        270        280        290        300 
MNNKFGLQRI LGDERSLLLL ARAIDPKQPN MMTEIVKILS AICIVGEENI LDKLLGAITT 

       310        320        330        340        350        360 
AAERNNRERF SPIVEGLENQ EALQLQVACM QFINALVTSP YELDFRIHLR NEFLRSGLKT 

       370        380        390        400        410        420 
MLPDLKEKEN DELDIQLKVF DENKEDDLTE LSHRLNDIRA EMDDMNEVYH LLYNMLKDTA 

       430        440        450        460        470        480 
AENYFLSILQ HFLLIRNDYY IRPQYYKIIE ECVSQIVLHC SGMDPDFKYR QRLDIDLTHL 

       490        500        510        520        530        540 
IDSCVNKAKV EESEQKAAEF SKKFDEEFTA RQEAQAELQK RDEKIKELEA EIQQLRTQAQ 

       550        560        570        580        590        600 
VLSSSSGIPG PPAAPPLPGV GPPPPPPAPP LPGGAPLPPP PPPLPGMMGI PPPPPPPLLF 

       610        620        630        640        650        660 
GGPPPPPPLG GVPPPPGISL NLPYGMKQKK MYKPEVSMKR INWSKIEPTE LSENCFWLRV 

       670        680        690        700        710        720 
KEDKFENPDL FAKLALNFAT QIKVQKNAEA LEEKKTGPTK KKVKELRILD PKTAQNLSIF 

       730        740        750        760        770        780 
LGSYRMPYED IRNVILEVNE DMLSEALIQN LVKHLPEQKI LNELAELKNE YDDLCEPEQF 

       790        800        810        820        830        840 
GVVMSSVKML QPRLSSILFK LTFEEHINNI KPSIIAVTLA CEELKKSESF NRLLELVLLV 

       850        860        870        880        890        900 
GNYMNSGSRN AQSLGFKINF LCKIRDTKSA DQKTTLLHFI ADICEEKYRD ILKFPEELEH 

       910        920        930        940        950        960 
VESASKVSAQ ILKSNLASME QQIVHLERDI KKFPQAENQH DKFVEKMTSF TKTAREQYEK 

       970        980        990       1000       1010       1020 
LSTMHNNMMK LYENLGEYFI FDSKTVSIEE FFGDLNNFRT LFLEAVRENN KRREMEEKTR 

      1030       1040       1050       1060       1070       1080 
RAKLAKEKAE QEKLERQKKK KQLIDINKEG DETGVMDNLL EALQSGAAFR DRRKRIPRNP 

      1090       1100 
DNRRVPLERS RSRHNGAISS K 

« Hide

Isoform 2 (DIA-12C) (DIA2B) [UniParc].

Checksum: D43A61A84A4B937F
Show »

FASTA1,096124,827
Isoform 3 (DIA2C) [UniParc].

Checksum: EE15E9AC8C949229
Show »

FASTA1,097125,043

References

« Hide 'large scale' references
[1]"A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility."
Bione S., Sala C., Manzini C., Arrigo G., Zuffardi O., Banfi S., Borsani G., Jonveaux P., Philippe C., Zuccotti M., Ballabio A., Toniolo D.
Am. J. Hum. Genet. 62:533-541(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, INVOLVEMENT IN POF2A.
[2]"RhoD regulates endosome dynamics through diaphanous-related formin and Src tyrosine kinase."
Gasman S., Kalaidzidis Y., Zerial M.
Nat. Cell Biol. 5:195-204(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 3), INTERACTION WITH RHOD, SUBCELLULAR LOCATION, FUNCTION.
[3]Erratum
Gasman S., Kalaidzidis Y., Zerial M.
Nat. Cell Biol. 5:680-680(2003)
[4]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"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].
[7]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y15909 mRNA. Translation: CAA75870.1.
Y15908 mRNA. Translation: CAA75869.1.
AL139809 expand/collapse EMBL AC list , AL031053, AL161624, AL391821, AL592157, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAI39928.1.
AL161624 expand/collapse EMBL AC list , AL031053, AL139809, AL391821, AL592157, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAI40915.1.
AL592157 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL391821, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAI40544.1.
AL606530 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL391821, AL592157, AL669876, Z86061 Genomic DNA. Translation: CAI39841.1.
Z86061 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL391821, AL592157, AL606530, AL669876 Genomic DNA. Translation: CAI42257.1.
AL031053 expand/collapse EMBL AC list , AL139809, AL161624, AL391821, AL592157, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAI42515.1.
AL669876 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL391821, AL592157, AL606530, Z86061 Genomic DNA. Translation: CAH71113.1.
AL669876 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL592157, AL606530, Z86061 Genomic DNA. Translation: CAH71114.1.
AL391821 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL592157, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAH71361.1.
AL592157 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAI40545.1.
AL606530 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL592157, AL669876, Z86061 Genomic DNA. Translation: CAI39842.1.
Z86061 expand/collapse EMBL AC list , AL031053, AL139809, AL161624, AL592157, AL606530, AL669876 Genomic DNA. Translation: CAI42258.1.
AL161624 expand/collapse EMBL AC list , AL031053, AL139809, AL592157, AL606530, AL669876, Z86061 Genomic DNA. Translation: CAI40916.1.
AL031053 Genomic DNA. Translation: CAB39108.2.
AL139809 Genomic DNA. Translation: CAD13477.2.
CCDSCCDS14467.1. [O60879-1]
CCDS14468.1. [O60879-2]
RefSeqNP_006720.1. NM_006729.4. [O60879-1]
NP_009293.1. NM_007309.3. [O60879-2]
UniGeneHs.226483.

3D structure databases

ProteinModelPortalO60879.
SMRO60879. Positions 106-477, 630-1070.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108074. 7 interactions.
DIPDIP-47261N.
IntActO60879. 3 interactions.
STRING9606.ENSP00000321348.

PTM databases

PhosphoSiteO60879.

Proteomic databases

MaxQBO60879.
PaxDbO60879.
PRIDEO60879.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324765; ENSP00000321348; ENSG00000147202. [O60879-1]
ENST00000373049; ENSP00000362140; ENSG00000147202. [O60879-2]
GeneID1730.
KEGGhsa:1730.
UCSCuc004eft.4. human. [O60879-2]
uc004efu.4. human. [O60879-1]

Organism-specific databases

CTD1730.
GeneCardsGC0XP095939.
HGNCHGNC:2877. DIAPH2.
HPACAB015461.
HPA005647.
MIM300108. gene.
300511. phenotype.
neXtProtNX_O60879.
Orphanet619. Primary ovarian failure.
PharmGKBPA27334.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149898.
HOGENOMHOG000293231.
HOVERGENHBG051357.
KOK05741.
OrthoDBEOG7G1V5D.
PhylomeDBO60879.
TreeFamTF315383.

Gene expression databases

ArrayExpressO60879.
BgeeO60879.
CleanExHS_DIAPH2.
GenevestigatorO60879.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR027644. DIAPH2.
IPR014767. Diaphanous_autoregulatory.
IPR010465. Drf_DAD.
IPR015425. FH2_Formin.
IPR010472. FH3_dom.
IPR010473. GTPase-bd.
IPR014768. GTPase-bd/formin_homology_3.
[Graphical view]
PANTHERPTHR23213:SF174. PTHR23213:SF174. 1 hit.
PfamPF06345. Drf_DAD. 1 hit.
PF06367. Drf_FH3. 1 hit.
PF06371. Drf_GBD. 1 hit.
PF02181. FH2. 1 hit.
[Graphical view]
SMARTSM00498. FH2. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
PROSITEPS51231. DAD. 1 hit.
PS51444. FH2. 1 hit.
PS51232. GBD_FH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDIAPH2.
GenomeRNAi1730.
NextBio7003.
PROO60879.
SOURCESearch...

Entry information

Entry nameDIAP2_HUMAN
AccessionPrimary (citable) accession number: O60879
Secondary accession number(s): A6NG19 expand/collapse secondary AC list , O60878, Q8WX06, Q8WX48, Q9UJL2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 141 of the entry and version 1 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

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