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Protein

Protein diaphanous homolog 3

Gene

DIAPH3

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

Functioni

Binds to GTP-bound form of Rho and to profilin. Acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization. It is required for cytokinesis, stress fiber formation, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-5663220 RHO GTPases Activate Formins

Names & Taxonomyi

Protein namesi
Recommended name:
Protein diaphanous homolog 3
Alternative name(s):
Diaphanous-related formin-3
Short name:
DRF3
MDia2
Gene namesi
Name:DIAPH3
Synonyms:DIAP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000139734.17
HGNCiHGNC:15480 DIAPH3
MIMi614567 gene
neXtProtiNX_Q9NSV4

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

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Auditory neuropathy, autosomal dominant, 1 (AUNA1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. A disease-causing mutation in the conserved 5'-UTR leads to increased protein expression (PubMed:20624953).1 Publication
Disease descriptionA form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem.
See also OMIM:609129

Keywords - Diseasei

Deafness, Neuropathy, Non-syndromic deafness

Organism-specific databases

DisGeNETi81624
MalaCardsiDIAPH3
MIMi609129 phenotype
OpenTargetsiENSG00000139734
Orphaneti90635 Autosomal dominant non-syndromic sensorineural deafness type DFNA
PharmGKBiPA27335

Polymorphism and mutation databases

BioMutaiDIAPH3
DMDMi158520000

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001948971 – 1193Protein diaphanous homolog 3Add BLAST1193

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei26PhosphoserineCombined sources1
Modified residuei68PhosphothreonineCombined sources1
Modified residuei77PhosphoserineCombined sources1
Modified residuei175PhosphoserineCombined sources1
Modified residuei624PhosphoserineCombined sources1
Modified residuei1093PhosphoserineCombined sources1
Modified residuei1179PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NSV4
PaxDbiQ9NSV4
PeptideAtlasiQ9NSV4
PRIDEiQ9NSV4
ProteomicsDBi82583
82584 [Q9NSV4-1]
82585 [Q9NSV4-2]
82586 [Q9NSV4-4]
82587 [Q9NSV4-5]
82588 [Q9NSV4-6]
82589 [Q9NSV4-7]

PTM databases

iPTMnetiQ9NSV4
PhosphoSitePlusiQ9NSV4

Expressioni

Developmental stagei

Increased expression in S phase and mitotic cells; levels decrease as cells enter in G0/G1 phase due to proteasomal degradation (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000139734
CleanExiHS_DIAPH3
GenevisibleiQ9NSV4 HS

Organism-specific databases

HPAiHPA032151

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi123559, 34 interactors
IntActiQ9NSV4, 13 interactors
MINTiQ9NSV4
STRINGi9606.ENSP00000383178

Structurei

Secondary structure

11193
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1184 – 1191Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5UWPX-ray2.05D1179-1193[»]
ProteinModelPortaliQ9NSV4
SMRiQ9NSV4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini114 – 476GBD/FH3PROSITE-ProRule annotationAdd BLAST363
Domaini561 – 631FH1Add BLAST71
Domaini636 – 1034FH2PROSITE-ProRule annotationAdd BLAST399
Domaini1057 – 1087DADPROSITE-ProRule annotationAdd BLAST31

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili497 – 554Sequence analysisAdd BLAST58
Coiled coili1013 – 1056Sequence analysisAdd BLAST44

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi561 – 636Pro-richAdd BLAST76

Domaini

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).By similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1924 Eukaryota
ENOG410Y29H LUCA
GeneTreeiENSGT00760000118986
HOVERGENiHBG051357
InParanoidiQ9NSV4
KOiK05745
OMAiKQMGRQL
OrthoDBiEOG091G0JR0
PhylomeDBiQ9NSV4
TreeFamiTF315383

Family and domain databases

Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR014767 DAD_dom
IPR010465 Drf_DAD
IPR015425 FH2_Formin
IPR010472 FH3_dom
IPR027654 Formin_DIAPH3
IPR014768 GBD/FH3_dom
IPR010473 GTPase-bd
PANTHERiPTHR23213:SF198 PTHR23213:SF198, 1 hit
PfamiView protein in Pfam
PF06345 Drf_DAD, 1 hit
PF06367 Drf_FH3, 1 hit
PF06371 Drf_GBD, 1 hit
PF02181 FH2, 1 hit
SMARTiView protein in SMART
SM01139 Drf_FH3, 1 hit
SM01140 Drf_GBD, 1 hit
SM00498 FH2, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS51231 DAD, 1 hit
PS51444 FH2, 1 hit
PS51232 GBD_FH3, 1 hit

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 3 (identifier: Q9NSV4-3) [UniParc]FASTAAdd to basket

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
MERHQPRLHH PAQGSAAGTP YPSSASLRGC RESKMPRRKG PQHPPPPSGP
60 70 80 90 100
EEPGEKRPKF HLNIRTLTDD MLDKFASIRI PGSKKERPPL PNLKTAFASS
110 120 130 140 150
DCSAAPLEMM ENFPKPLSEN ELLELFEKMM EDMNLNEDKK APLREKDFSI
160 170 180 190 200
KKEMVMQYIN TASKTGSLKR SRQISPQEFI HELKMGSADE RLVTCLESLR
210 220 230 240 250
VSLTSNPVSW VESFGHEGLG LLLDILEKLI SGKIQEKVVK KNQHKVIQCL
260 270 280 290 300
KALMNTQYGL ERIMSEERSL SLLAKAVDPR HPNMMTDVVK LLSAVCIVGE
310 320 330 340 350
ESILEEVLEA LTSAGEEKKI DRFFCIVEGL RHNSVQLQVA CMQLINALVT
360 370 380 390 400
SPDDLDFRLH IRNEFMRCGL KEILPNLKCI KNDGLDIQLK VFDEHKEEDL
410 420 430 440 450
FELSHRLEDI RAELDEAYDV YNMVWSTVKE TRAEGYFISI LQHLLLIRND
460 470 480 490 500
YFIRQQYFKL IDECVSQIVL HRDGMDPDFT YRKRLDLDLT QFVDICIDQA
510 520 530 540 550
KLEEFEEKAS ELYKKFEKEF TDHQETQAEL QKKEAKINEL QAELQAFKSQ
560 570 580 590 600
FGALPADCNI PLPPSKEGGT GHSALPPPPP LPSGGGVPPP PPPPPPPPLP
610 620 630 640 650
GMRMPFSGPV PPPPPLGFLG GQNSPPLPIL PFGLKPKKEF KPEISMRRLN
660 670 680 690 700
WLKIRPHEMT ENCFWIKVNE NKYENVDLLC KLENTFCCQQ KERREEEDIE
710 720 730 740 750
EKKSIKKKIK ELKFLDSKIA QNLSIFLSSF RVPYEEIRMM ILEVDETRLA
760 770 780 790 800
ESMIQNLIKH LPDQEQLNSL SQFKSEYSNL CEPEQFVVVM SNVKRLRPRL
810 820 830 840 850
SAILFKLQFE EQVNNIKPDI MAVSTACEEI KKSKSFSKLL ELVLLMGNYM
860 870 880 890 900
NAGSRNAQTF GFNLSSLCKL KDTKSADQKT TLLHFLVEIC EEKYPDILNF
910 920 930 940 950
VDDLEPLDKA SKVSVETLEK NLRQMGRQLQ QLEKELETFP PPEDLHDKFV
960 970 980 990 1000
TKMSRFVISA KEQYETLSKL HENMEKLYQS IIGYYAIDVK KVSVEDFLTD
1010 1020 1030 1040 1050
LNNFRTTFMQ AIKENIKKRE AEEKEKRVRI AKELAERERL ERQQKKKRLL
1060 1070 1080 1090 1100
EMKTEGDETG VMDNLLEALQ SGAAFRDRRK RTPMPKDVRQ SLSPMSQRPV
1110 1120 1130 1140 1150
LKVCNHENQK VQLTEGSRSH YNINCNSTRT PVAKELNYNL DTHTSTGRIK
1160 1170 1180 1190
AAEKKEACNV ESNRKKETEL LGSFSKNESV PEVEALLARL RAL
Length:1,193
Mass (Da):136,926
Last modified:September 11, 2007 - v4
Checksum:iABCA4E859873F9E7
GO
Isoform 1 (identifier: Q9NSV4-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-263: Missing.
     1107-1112: ENQKVQ → GNKPYL
     1113-1193: Missing.

Show »
Length:849
Mass (Da):98,140
Checksum:i5CE99DEE93AC833C
GO
Isoform 2 (identifier: Q9NSV4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-263: Missing.
     913-956: VSVETLEKNL...DKFVTKMSRF → GLCLFKKHFM...HSVFIPNISF
     957-1193: Missing.

Show »
Length:691
Mass (Da):79,445
Checksum:iCDFF84D86D4B66DF
GO
Isoform 4 (identifier: Q9NSV4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     61-71: Missing.

Show »
Length:1,182
Mass (Da):135,615
Checksum:i9169ACD33B8FB00D
GO
Isoform 5 (identifier: Q9NSV4-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     61-71: Missing.
     131-165: Missing.

Show »
Length:1,147
Mass (Da):131,487
Checksum:i4286EEB6F00A3F01
GO
Isoform 6 (identifier: Q9NSV4-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     61-71: Missing.
     72-130: Missing.

Show »
Length:1,123
Mass (Da):128,994
Checksum:i4623CCC9C5D433C6
GO
Isoform 7 (identifier: Q9NSV4-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1107-1112: ENQKVQ → GNKPYL
     1113-1193: Missing.

Show »
Length:1,112
Mass (Da):127,856
Checksum:iDCB5192396280A30
GO

Sequence cautioni

The sequence AAW73254 differs from that shown. Reason: Frameshift at position 1147.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55E → G in BAE96352 (Ref. 3) Curated1
Sequence conflicti128K → R in BAC03793 (PubMed:14702039).Curated1
Sequence conflicti274A → V in AAH34952 (PubMed:15489334).Curated1
Sequence conflicti330L → P in BAE96351 (Ref. 3) Curated1
Sequence conflicti588P → L in BAC03793 (PubMed:14702039).Curated1
Sequence conflicti613P → L in BAE96351 (Ref. 3) Curated1
Sequence conflicti669N → K in CAE46204 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049097363N → S. Corresponds to variant dbSNP:rs36084898EnsemblClinVar.1
Natural variantiVAR_049098773F → L. Corresponds to variant dbSNP:rs35579086EnsemblClinVar.1
Natural variantiVAR_0490991041E → G. Corresponds to variant dbSNP:rs7491389Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0159581 – 263Missing in isoform 1 and isoform 2. 2 PublicationsAdd BLAST263
Alternative sequenceiVSP_02777461 – 71Missing in isoform 4, isoform 5 and isoform 6. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_02777572 – 130Missing in isoform 6. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_027776131 – 165Missing in isoform 5. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_001574913 – 956VSVET…KMSRF → GLCLFKKHFMALIFSAKRLK IIPFICMYFPLSHSVFIPNI SF in isoform 2. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_001575957 – 1193Missing in isoform 2. 1 PublicationAdd BLAST237
Alternative sequenceiVSP_0277771107 – 1112ENQKVQ → GNKPYL in isoform 7 and isoform 1. 2 Publications6
Alternative sequenceiVSP_0277781113 – 1193Missing in isoform 7 and isoform 1. 2 PublicationsAdd BLAST81

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY750055 mRNA Translation: AAW73254.1 Frameshift.
AY818645 mRNA Translation: AAW78862.1
AB244756 mRNA Translation: BAE96350.1
AB244757 mRNA Translation: BAE96351.1
AB244758 mRNA Translation: BAE96352.1
AL137718 mRNA Translation: CAB70890.1
BX649186 mRNA Translation: CAE46204.1
AL354829 Genomic DNA No translation available.
AL356502 Genomic DNA No translation available.
AL359266 Genomic DNA No translation available.
AL390878 Genomic DNA No translation available.
BC034952 mRNA Translation: AAH34952.1
BC048963 mRNA Translation: AAH48963.1
BC068504 mRNA Translation: AAH68504.1
AK092024 mRNA Translation: BAC03793.1
CCDSiCCDS41898.1 [Q9NSV4-3]
CCDS58294.1 [Q9NSV4-6]
CCDS58295.1 [Q9NSV4-5]
CCDS58296.1 [Q9NSV4-4]
CCDS58297.1 [Q9NSV4-7]
CCDS73579.1 [Q9NSV4-2]
CCDS73580.1 [Q9NSV4-1]
RefSeqiNP_001035982.1, NM_001042517.1 [Q9NSV4-3]
NP_001245295.1, NM_001258366.1 [Q9NSV4-4]
NP_001245296.1, NM_001258367.1 [Q9NSV4-5]
NP_001245297.1, NM_001258368.1 [Q9NSV4-6]
NP_001245298.1, NM_001258369.1 [Q9NSV4-7]
NP_001245299.1, NM_001258370.1 [Q9NSV4-2]
NP_112194.2, NM_030932.3 [Q9NSV4-1]
UniGeneiHs.283127

Genome annotation databases

EnsembliENST00000267215; ENSP00000267215; ENSG00000139734 [Q9NSV4-7]
ENST00000377908; ENSP00000367141; ENSG00000139734 [Q9NSV4-4]
ENST00000400319; ENSP00000383173; ENSG00000139734 [Q9NSV4-6]
ENST00000400320; ENSP00000383174; ENSG00000139734 [Q9NSV4-5]
ENST00000400324; ENSP00000383178; ENSG00000139734 [Q9NSV4-3]
ENST00000465066; ENSP00000478137; ENSG00000139734 [Q9NSV4-1]
ENST00000498416; ENSP00000479091; ENSG00000139734 [Q9NSV4-2]
GeneIDi81624
KEGGihsa:81624
UCSCiuc001vht.6 human [Q9NSV4-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDIAP3_HUMAN
AccessioniPrimary (citable) accession number: Q9NSV4
Secondary accession number(s): A2A3B8
, A2A3B9, A2A3C0, Q18P99, Q18PA0, Q18PA1, Q2KPB6, Q3ZK23, Q5JTP8, Q5T2S7, Q5XKF6, Q6MZF0, Q6NUP0, Q86VS4, Q8NAV4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: September 11, 2007
Last modified: June 20, 2018
This is version 172 of the entry and version 4 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

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