DIAP2_HUMAN
ID DIAP2_HUMAN Reviewed; 1101 AA.
AC O60879; A6NG19; O60878; Q8WX06; Q8WX48; Q9UJL2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Protein diaphanous homolog 2;
DE AltName: Full=Diaphanous-related formin-2;
DE Short=DRF2;
GN Name=DIAPH2; Synonyms=DIA;
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 [MRNA], ALTERNATIVE SPLICING, AND INVOLVEMENT IN POF2A.
RX PubMed=9497258; DOI=10.1086/301761;
RA Bione S., Sala C., Manzini C., Arrigo G., Zuffardi O., Banfi S.,
RA Borsani G., Jonveaux P., Philippe C., Zuccotti M., Ballabio A., Toniolo D.;
RT "A human homologue of the Drosophila melanogaster diaphanous gene is
RT disrupted in a patient with premature ovarian failure: evidence for
RT conserved function in oogenesis and implications for human sterility.";
RL Am. J. Hum. Genet. 62:533-541(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 3), INTERACTION WITH RHOD, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=12577064; DOI=10.1038/ncb935;
RA Gasman S., Kalaidzidis Y., Zerial M.;
RT "RhoD regulates endosome dynamics through diaphanous-related formin and Src
RT tyrosine kinase.";
RL Nat. Cell Biol. 5:195-204(2003).
RN [3]
RP ERRATUM OF PUBMED:12577064.
RA Gasman S., Kalaidzidis Y., Zerial M.;
RL Nat. Cell Biol. 5:680-680(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Could be involved in oogenesis. Involved in the regulation of
CC endosome dynamics. Implicated in a novel signal transduction pathway,
CC in which isoform 3 and CSK are sequentially activated by RHOD to
CC regulate the motility of early endosomes through interactions with the
CC actin cytoskeleton. {ECO:0000269|PubMed:12577064}.
CC -!- SUBUNIT: Isoform 3 interacts with RHOD in the GTP-bound form.
CC {ECO:0000269|PubMed:12577064}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol. Early endosome.
CC Note=Isoform 3 is cytosolic but when coexpressed with RHOD, the 2
CC proteins colocalize to early endosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=DIA-156;
CC IsoId=O60879-1; Sequence=Displayed;
CC Name=2; Synonyms=DIA-12C, DIA2B;
CC IsoId=O60879-2; Sequence=VSP_001573;
CC Name=3; Synonyms=DIA2C;
CC IsoId=O60879-3; Sequence=VSP_012955, VSP_012956;
CC -!- TISSUE SPECIFICITY: Expressed in testis, ovary, small intestine,
CC prostate, lung, liver, kidney and leukocytes.
CC -!- DEVELOPMENTAL STAGE: Expressed from E16 in ovary and testis and during
CC P6-P16 during differentiation of ovarian follicles.
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 -!- DISEASE: Premature ovarian failure 2A (POF2A) [MIM:300511]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:9497258}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the formin homology family. Diaphanous
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y15909; CAA75870.1; -; mRNA.
DR EMBL; Y15908; CAA75869.1; -; mRNA.
DR EMBL; AL031053; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161624; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592157; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL606530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL669876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z86061; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS14467.1; -. [O60879-1]
DR CCDS; CCDS14468.1; -. [O60879-2]
DR RefSeq; NP_006720.1; NM_006729.4. [O60879-1]
DR RefSeq; NP_009293.1; NM_007309.3. [O60879-2]
DR AlphaFoldDB; O60879; -.
DR SMR; O60879; -.
DR BioGRID; 108074; 36.
DR DIP; DIP-47261N; -.
DR IntAct; O60879; 10.
DR MINT; O60879; -.
DR STRING; 9606.ENSP00000321348; -.
DR iPTMnet; O60879; -.
DR PhosphoSitePlus; O60879; -.
DR BioMuta; DIAPH2; -.
DR EPD; O60879; -.
DR jPOST; O60879; -.
DR MassIVE; O60879; -.
DR MaxQB; O60879; -.
DR PaxDb; O60879; -.
DR PeptideAtlas; O60879; -.
DR PRIDE; O60879; -.
DR ProteomicsDB; 49639; -. [O60879-1]
DR ProteomicsDB; 49640; -. [O60879-2]
DR ProteomicsDB; 49641; -. [O60879-3]
DR Antibodypedia; 471; 284 antibodies from 34 providers.
DR DNASU; 1730; -.
DR Ensembl; ENST00000324765.13; ENSP00000321348.8; ENSG00000147202.19. [O60879-1]
DR Ensembl; ENST00000373049.8; ENSP00000362140.4; ENSG00000147202.19. [O60879-2]
DR GeneID; 1730; -.
DR KEGG; hsa:1730; -.
DR MANE-Select; ENST00000324765.13; ENSP00000321348.8; NM_006729.5; NP_006720.1.
DR UCSC; uc004eft.5; human. [O60879-1]
DR CTD; 1730; -.
DR DisGeNET; 1730; -.
DR GeneCards; DIAPH2; -.
DR HGNC; HGNC:2877; DIAPH2.
DR HPA; ENSG00000147202; Low tissue specificity.
DR MalaCards; DIAPH2; -.
DR MIM; 300108; gene.
DR MIM; 300511; phenotype.
DR neXtProt; NX_O60879; -.
DR OpenTargets; ENSG00000147202; -.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR PharmGKB; PA27334; -.
DR VEuPathDB; HostDB:ENSG00000147202; -.
DR eggNOG; KOG1924; Eukaryota.
DR GeneTree; ENSGT00940000157822; -.
DR InParanoid; O60879; -.
DR OrthoDB; 1204639at2759; -.
DR PhylomeDB; O60879; -.
DR TreeFam; TF315383; -.
DR PathwayCommons; O60879; -.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle. [O60879-3]
DR Reactome; R-HSA-9035034; RHOF GTPase cycle.
DR SignaLink; O60879; -.
DR SIGNOR; O60879; -.
DR BioGRID-ORCS; 1730; 14 hits in 696 CRISPR screens.
DR ChiTaRS; DIAPH2; human.
DR GeneWiki; DIAPH2; -.
DR GenomeRNAi; 1730; -.
DR Pharos; O60879; Tbio.
DR PRO; PR:O60879; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O60879; protein.
DR Bgee; ENSG00000147202; Expressed in buccal mucosa cell and 198 other tissues.
DR ExpressionAtlas; O60879; baseline and differential.
DR Genevisible; O60879; HS.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0030041; P:actin filament polymerization; IBA:GO_Central.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.20.40; -; 1.
DR Gene3D; 1.20.58.2220; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014767; DAD_dom.
DR InterPro; IPR044933; DIA_GBD_sf.
DR InterPro; IPR027644; DIAPH2.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR InterPro; IPR010472; FH3_dom.
DR InterPro; IPR014768; GBD/FH3_dom.
DR InterPro; IPR010473; GTPase-bd.
DR PANTHER; PTHR45691:SF3; PTHR45691:SF3; 1.
DR Pfam; PF06367; Drf_FH3; 1.
DR Pfam; PF06371; Drf_GBD; 1.
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 Acetylation; Alternative splicing; Coiled coil; Cytoplasm;
KW Developmental protein; Differentiation; Endosome; Oogenesis;
KW Premature ovarian failure; Reference proteome; Repeat.
FT CHAIN 1..1101
FT /note="Protein diaphanous homolog 2"
FT /id="PRO_0000194895"
FT DOMAIN 98..464
FT /note="GBD/FH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00579"
FT DOMAIN 549..623
FT /note="FH1"
FT DOMAIN 628..1028
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT DOMAIN 1051..1081
FT /note="DAD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00577"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 536..594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1010..1048
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1070..1101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 366..418
FT /evidence="ECO:0000255"
FT COILED 487..547
FT /evidence="ECO:0000255"
FT COILED 903..1053
FT /evidence="ECO:0000255"
FT COMPBIAS 29..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..594
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1070..1095
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT VAR_SEQ 45..55
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_012955"
FT VAR_SEQ 149
FT /note="S -> SIVGSKVT (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_012956"
FT VAR_SEQ 1081..1101
FT /note="DNRRVPLERSRSRHNGAISSK -> VVNHPCATRANPRSAT (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001573"
FT VARIANT 425
FT /note="F -> L (in dbSNP:rs20361)"
FT /id="VAR_049095"
FT VARIANT 426
FT /note="L -> V (in dbSNP:rs20361)"
FT /id="VAR_049096"
SQ SEQUENCE 1101 AA; 125569 MW; 399F1C292D79188B CRC64;
MEQPGAAASG AGGGSEEPGG GRSNKRSAGN RAANEEETKN KPKLNIQIKT LADDVRDRIT
SFRKSTVKKE KPLIQHPIDS QVAMSEFPAA QPLYDERSLN LSEKEVLDLF EKMMEDMNLN
EEKKAPLRNK DFTTKREMVV QYISATAKSG GLKNSKHECT LSSQEYVHEL RSGISDEKLL
NCLESLRVSL TSNPVSWVNN FGHEGLGLLL DELEKLLDKK QQENIDKKNQ YKLIQCLKAF
MNNKFGLQRI LGDERSLLLL ARAIDPKQPN MMTEIVKILS AICIVGEENI LDKLLGAITT
AAERNNRERF SPIVEGLENQ EALQLQVACM QFINALVTSP YELDFRIHLR NEFLRSGLKT
MLPDLKEKEN DELDIQLKVF DENKEDDLTE LSHRLNDIRA EMDDMNEVYH LLYNMLKDTA
AENYFLSILQ HFLLIRNDYY IRPQYYKIIE ECVSQIVLHC SGMDPDFKYR QRLDIDLTHL
IDSCVNKAKV EESEQKAAEF SKKFDEEFTA RQEAQAELQK RDEKIKELEA EIQQLRTQAQ
VLSSSSGIPG PPAAPPLPGV GPPPPPPAPP LPGGAPLPPP PPPLPGMMGI PPPPPPPLLF
GGPPPPPPLG GVPPPPGISL NLPYGMKQKK MYKPEVSMKR INWSKIEPTE LSENCFWLRV
KEDKFENPDL FAKLALNFAT QIKVQKNAEA LEEKKTGPTK KKVKELRILD PKTAQNLSIF
LGSYRMPYED IRNVILEVNE DMLSEALIQN LVKHLPEQKI LNELAELKNE YDDLCEPEQF
GVVMSSVKML QPRLSSILFK LTFEEHINNI KPSIIAVTLA CEELKKSESF NRLLELVLLV
GNYMNSGSRN AQSLGFKINF LCKIRDTKSA DQKTTLLHFI ADICEEKYRD ILKFPEELEH
VESASKVSAQ ILKSNLASME QQIVHLERDI KKFPQAENQH DKFVEKMTSF TKTAREQYEK
LSTMHNNMMK LYENLGEYFI FDSKTVSIEE FFGDLNNFRT LFLEAVRENN KRREMEEKTR
RAKLAKEKAE QEKLERQKKK KQLIDINKEG DETGVMDNLL EALQSGAAFR DRRKRIPRNP
DNRRVPLERS RSRHNGAISS K
