Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Differentially expressed in FDCP 6 homolog

Gene

DEF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42. Can regulate cell morphology in cooperation with activated RAC1. Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling (By similarity).By similarity2 Publications

Names & Taxonomyi

Protein namesi
Recommended name:
Differentially expressed in FDCP 6 homolog
Short name:
DEF-6
Alternative name(s):
IRF4-binding protein
Gene namesi
Name:DEF6
Synonyms:IBP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:2760. DEF6.

Subcellular locationi

GO - Cellular componenti

  • cytoskeleton Source: UniProtKB-SubCell
  • filopodium Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi18 – 181L → N: Abolishes interaction with RAC1. 1 Publication
Mutagenesisi31 – 333LKV → NKS: Abolishes interaction with RAC1. 1 Publication
Mutagenesisi210 – 2101Y → F: Loss of phosphorylation by LCK and abolition of PtdInsP3 binding. 1 Publication
Mutagenesisi225 – 2262KR → AA: Abolishes PtdInsP3 binding. 1 Publication
Mutagenesisi230 – 2312RR → AA: Abolishes PtdInsP3 binding. 1 Publication
Mutagenesisi236 – 2361R → C: Abolishes PtdInsP3 binding. 1 Publication

Organism-specific databases

PharmGKBiPA27237.

Polymorphism and mutation databases

BioMutaiDEF6.
DMDMi74761430.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 631631Differentially expressed in FDCP 6 homologPRO_0000294522Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei210 – 2101Phosphotyrosine1 Publication
Modified residuei225 – 2251N6-acetyllysineCombined sources
Modified residuei590 – 5901PhosphoserineCombined sources

Post-translational modificationi

Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response to T-cell activation.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H4E7.
MaxQBiQ9H4E7.
PaxDbiQ9H4E7.
PRIDEiQ9H4E7.

PTM databases

iPTMnetiQ9H4E7.
PhosphoSiteiQ9H4E7.

Expressioni

Tissue specificityi

Broadly expressed in the immune system and can be detected in T and B-cells.1 Publication

Gene expression databases

BgeeiQ9H4E7.
CleanExiHS_DEF6.
ExpressionAtlasiQ9H4E7. baseline and differential.
GenevisibleiQ9H4E7. HS.

Organism-specific databases

HPAiHPA038975.
HPA038976.

Interactioni

Subunit structurei

Interacts with ZAP70 (By similarity). Interacts with IRF4, activated RAC1 and F-actin. Both the phosphorylated and non-phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC42EP1Q005873EBI-745369,EBI-744130
EIF4ENIF1Q9NRA83EBI-745369,EBI-301024
HOMEZQ8IX15-33EBI-745369,EBI-10172004
PBXIP1Q96AQ63EBI-745369,EBI-740845
PLSCR1O151623EBI-745369,EBI-740019
PTK2I6L9963EBI-745369,EBI-10181089
TCF4P158843EBI-745369,EBI-533224

Protein-protein interaction databases

BioGridi119099. 33 interactions.
IntActiQ9H4E7. 11 interactions.
MINTiMINT-1471710.
STRINGi9606.ENSP00000319831.

Structurei

3D structure databases

ProteinModelPortaliQ9H4E7.
SMRiQ9H4E7. Positions 217-319.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini216 – 31297PHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi57 – 604Poly-Asp
Compositional biasi331 – 497167Glu-richAdd
BLAST

Domaini

The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding.1 Publication

Sequence similaritiesi

Contains 1 PH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IG09. Eukaryota.
ENOG410Z316. LUCA.
GeneTreeiENSGT00390000005512.
HOGENOMiHOG000285974.
HOVERGENiHBG053201.
InParanoidiQ9H4E7.
OMAiYLWKKGQ.
OrthoDBiEOG7H1JK5.
PhylomeDBiQ9H4E7.
TreeFamiTF333160.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 2 hits.
SSF50729. SSF50729. 2 hits.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9H4E7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALRKELLKS IWYAFTALDV EKSGKVSKSQ LKVLSHNLYT VLHIPHDPVA
60 70 80 90 100
LEEHFRDDDD GPVSSQGYMP YLNKYILDKV EEGAFVKEHF DELCWTLTAK
110 120 130 140 150
KNYRADSNGN SMLSNQDAFR LWCLFNFLSE DKYPLIMVPD EVEYLLKKVL
160 170 180 190 200
SSMSLEVSLG ELEELLAQEA QVAQTTGGLS VWQFLELFNS GRCLRGVGRD
210 220 230 240 250
TLSMAIHEVY QELIQDVLKQ GYLWKRGHLR RNWAERWFQL QPSCLCYFGS
260 270 280 290 300
EECKEKRGII PLDAHCCVEV LPDRDGKRCM FCVKTANRTY EMSASDTRQR
310 320 330 340 350
QEWTAAIQMA IRLQAEGKTS LHKDLKQKRR EQREQRERRR AAKEEELLRL
360 370 380 390 400
QQLQEEKERK LQELELLQEA QRQAERLLQE EEERRRSQHR ELQQALEGQL
410 420 430 440 450
REAEQARASM QAEMELKEEE AARQRQRIKE LEEMQQRLQE ALQLEVKARR
460 470 480 490 500
DEESVRIAQT RLLEEEEEKL KQLMQLKEEQ ERYIERAQQE KEELQQEMAQ
510 520 530 540 550
QSRSLQQAQQ QLEEVRQNRQ RADEDVEAAQ RKLRQASTNV KHWNVQMNRL
560 570 580 590 600
MHPIEPGDKR PVTSSSFSGF QPPLLAHRDS SLKRLTRWGS QGNRTPSPNS
610 620 630
NEQQKSLNGG DEAPAPASTP QEDKLDPAPE N
Length:631
Mass (Da):73,910
Last modified:March 1, 2001 - v1
Checksum:i466A9A3D6D5CB8D8
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti287 – 2871N → T.1 Publication
Corresponds to variant rs2395617 [ dbSNP | Ensembl ].
VAR_033193
Natural varianti578 – 5781R → H.
Corresponds to variant rs9296146 [ dbSNP | Ensembl ].
VAR_033194

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY241694 mRNA. Translation: AAO91767.1.
AJ276095 mRNA. Translation: CAC08450.1.
Z97832 Genomic DNA. Translation: CAI20190.1.
CCDSiCCDS4802.1.
RefSeqiNP_071330.3. NM_022047.3.
UniGeneiHs.15476.

Genome annotation databases

EnsembliENST00000316637; ENSP00000319831; ENSG00000023892.
GeneIDi50619.
KEGGihsa:50619.
UCSCiuc003okk.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY241694 mRNA. Translation: AAO91767.1.
AJ276095 mRNA. Translation: CAC08450.1.
Z97832 Genomic DNA. Translation: CAI20190.1.
CCDSiCCDS4802.1.
RefSeqiNP_071330.3. NM_022047.3.
UniGeneiHs.15476.

3D structure databases

ProteinModelPortaliQ9H4E7.
SMRiQ9H4E7. Positions 217-319.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119099. 33 interactions.
IntActiQ9H4E7. 11 interactions.
MINTiMINT-1471710.
STRINGi9606.ENSP00000319831.

PTM databases

iPTMnetiQ9H4E7.
PhosphoSiteiQ9H4E7.

Polymorphism and mutation databases

BioMutaiDEF6.
DMDMi74761430.

Proteomic databases

EPDiQ9H4E7.
MaxQBiQ9H4E7.
PaxDbiQ9H4E7.
PRIDEiQ9H4E7.

Protocols and materials databases

DNASUi50619.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316637; ENSP00000319831; ENSG00000023892.
GeneIDi50619.
KEGGihsa:50619.
UCSCiuc003okk.4. human.

Organism-specific databases

CTDi50619.
GeneCardsiDEF6.
H-InvDBHIX0005803.
HGNCiHGNC:2760. DEF6.
HPAiHPA038975.
HPA038976.
MIMi610094. gene.
neXtProtiNX_Q9H4E7.
PharmGKBiPA27237.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG09. Eukaryota.
ENOG410Z316. LUCA.
GeneTreeiENSGT00390000005512.
HOGENOMiHOG000285974.
HOVERGENiHBG053201.
InParanoidiQ9H4E7.
OMAiYLWKKGQ.
OrthoDBiEOG7H1JK5.
PhylomeDBiQ9H4E7.
TreeFamiTF333160.

Miscellaneous databases

ChiTaRSiDEF6. human.
GeneWikiiDEF6.
GenomeRNAii50619.
PROiQ9H4E7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H4E7.
CleanExiHS_DEF6.
ExpressionAtlasiQ9H4E7. baseline and differential.
GenevisibleiQ9H4E7. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 2 hits.
SSF50729. SSF50729. 2 hits.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly expressed in the immune system."
    Gupta S., Lee A.E., Hu C., Fanzo J.C., Goldberg I., Cattoretti G., Pernis A.B.
    Hum. Immunol. 64:389-401(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH IRF4, VARIANT THR-287.
    Tissue: Lymph node.
  2. "DEF6, a novel PH-DH-like domain protein, is an upstream activator of the Rho GTPases Rac1, Cdc42, and RhoA."
    Mavrakis K.J., McKinlay K.J., Jones P., Sablitzky F.
    Exp. Cell Res. 294:335-344(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH F-ACTIN, PTDINSP3-BINDING.
  3. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "T cell receptor engagement leads to the recruitment of IBP, a novel guanine nucleotide exchange factor, to the immunological synapse."
    Gupta S., Fanzo J.C., Hu C., Cox D., Jang S.Y., Lee A.E., Greenberg S., Pernis A.B.
    J. Biol. Chem. 278:43541-43549(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, PTDINSP3-BINDING, MUTAGENESIS OF TYR-210 AND ARG-236.
  5. "Cooperation of DEF6 with activated Rac in regulating cell morphology."
    Oka T., Ihara S., Fukui Y.
    J. Biol. Chem. 282:2011-2018(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RAC1, PTDINSP3-BINDING, DOMAIN, MUTAGENESIS OF LEU-18; 31-LEU--VAL-33; 225-LYS-ARG-226 AND 230-ARG-ARG-231.
  6. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-590, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  7. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-225, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiDEFI6_HUMAN
AccessioniPrimary (citable) accession number: Q9H4E7
Secondary accession number(s): Q86VF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 10, 2007
Last sequence update: March 1, 2001
Last modified: June 8, 2016
This is version 117 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.