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Protein

IQ motif and SEC7 domain-containing protein 1

Gene

IQSEC1

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

Functioni

Guanine nucleotide exchange factor for ARF1 and ARF6 (PubMed:24058294). Guanine nucleotide exchange factor activity is enhanced by lipid binding (PubMed:24058294). Accelerates GTP binding by ARFs of all three classes. Guanine nucleotide exchange protein for ARF6, mediating internalisation of beta-1 integrin.3 Publications

GO - Molecular functioni

  1. ARF guanyl-nucleotide exchange factor activity Source: GO_Central

GO - Biological processi

  1. actin cytoskeleton organization Source: GO_Central
  2. positive regulation of GTPase activity Source: GOC
  3. regulation of ARF protein signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Lipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
IQ motif and SEC7 domain-containing protein 1
Alternative name(s):
ADP-ribosylation factors guanine nucleotide-exchange protein 100
ADP-ribosylation factors guanine nucleotide-exchange protein 2
Brefeldin-resistant Arf-GEF 2 protein1 Publication
Short name:
BRAG21 Publication
Gene namesi
Name:IQSEC1
Synonyms:ARFGEP100, BRAG2, KIAA0763
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:29112. IQSEC1.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: At steady state, may be preferentially cytosolic.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. membrane Source: UniProtKB
  3. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi620 – 6201E → K: Abolishes guanosine nucleotide exchange factor activity. 1 Publication

Organism-specific databases

PharmGKBiPA128394566.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 963963IQ motif and SEC7 domain-containing protein 1PRO_0000245606Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei180 – 1801Phosphoserine2 Publications
Modified residuei253 – 2531Phosphoserine1 Publication
Modified residuei512 – 5121Phosphoserine3 Publications
Modified residuei515 – 5151PhosphoserineBy similarity
Modified residuei911 – 9111Phosphotyrosine1 Publication
Modified residuei924 – 9241Phosphoserine1 Publication
Modified residuei925 – 9251Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ6DN90.
PaxDbiQ6DN90.
PRIDEiQ6DN90.

Expressioni

Tissue specificityi

Expressed in brain, ovary, heart, lung, liver, kidney and leukocytes. Moderate expression was also detected in lung, skeletal muscle, placenta, small intestine, pancreas, spleen and testis.2 Publications

Gene expression databases

BgeeiQ6DN90.
CleanExiHS_IQSEC1.
GenevestigatoriQ6DN90.

Organism-specific databases

HPAiHPA038143.
HPA038144.

Interactioni

Subunit structurei

Interacts with ARF1 and ARF6.2 Publications

Protein-protein interaction databases

BioGridi115250. 9 interactions.
IntActiQ6DN90. 6 interactions.
STRINGi9606.ENSP00000273221.

Structurei

Secondary structure

1
963
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi522 – 53716Combined sources
Helixi539 – 54810Combined sources
Helixi556 – 56510Combined sources
Helixi571 – 5788Combined sources
Helixi584 – 59512Combined sources
Helixi604 – 61411Combined sources
Helixi621 – 63818Combined sources
Helixi640 – 6467Combined sources
Helixi650 – 66718Combined sources
Turni669 – 6713Combined sources
Beta strandi673 – 6764Combined sources
Helixi679 – 6857Combined sources
Turni686 – 6894Combined sources
Helixi697 – 70913Combined sources
Helixi718 – 72811Combined sources
Beta strandi753 – 7619Combined sources
Turni771 – 7744Combined sources
Beta strandi775 – 7839Combined sources
Beta strandi785 – 7895Combined sources
Beta strandi803 – 8064Combined sources
Beta strandi811 – 8166Combined sources
Beta strandi824 – 8296Combined sources
Beta strandi832 – 8343Combined sources
Beta strandi837 – 8437Combined sources
Helixi847 – 87832Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QWMX-ray2.39A743-880[»]
4C0AX-ray3.30A/B/E/F512-885[»]
ProteinModelPortaliQ6DN90.
SMRiQ6DN90. Positions 515-880.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini134 – 16330IQPROSITE-ProRule annotationAdd
BLAST
Domaini517 – 710194SEC7PROSITE-ProRule annotationAdd
BLAST
Domaini774 – 86693PHAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili848 – 87932Sequence AnalysisAdd
BLAST

Domaini

The PH domain mediates interaction with lipid membranes that contain phosphatidylinositol-4,5-bisphosphate, but does not bind membranes that lack phosphatidylinositol-4,5-bisphosphate.1 Publication

Sequence similaritiesi

Belongs to the BRAG family.Curated
Contains 1 IQ domain.PROSITE-ProRule annotation
Contains 1 PH domain.Curated
Contains 1 SEC7 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG5307.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000113099.
HOVERGENiHBG056324.
InParanoidiQ6DN90.
KOiK12495.
PhylomeDBiQ6DN90.
TreeFamiTF323811.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000048. IQ_motif_EF-hand-BS.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamiPF01369. Sec7. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48425. SSF48425. 1 hit.
PROSITEiPS50096. IQ. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6DN90-1) [UniParc]FASTAAdd to basket

Also known as: BRAG2b

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
MWCLHCNSER TQSLLELELD SGVEGEAPSS ETGTSLDSPS AYPQGPLVPG
60 70 80 90 100
SSLSPDHYEH TSVGAYGLYS GPPGQQQRTR RPKLQHSTSI LRKQAEEEAI
110 120 130 140 150
KRSRSLSESY ELSSDLQDKQ VEMLERKYGG RLVTRHAART IQTAFRQYQM
160 170 180 190 200
NKNFERLRSS MSENRMSRRI VLSNMRMQFS FEGPEKVHSS YFEGKQVSVT
210 220 230 240 250
NDGSQLGALV SPECGDLSEP TTLKSPAPSS DFADAITELE DAFSRQVKSL
260 270 280 290 300
AESIDDALNC RSLHTEEAPA LDAARARDTE PQTALHGMDH RKLDEMTASY
310 320 330 340 350
SDVTLYIDEE ELSPPLPLSQ AGDRPSSTES DLRLRAGGAA PDYWALAHKE
360 370 380 390 400
DKADTDTSCR STPSLERQEQ RLRVEHLPLL TIEPPSDSSV DLSDRSERGS
410 420 430 440 450
LKRQSAYERS LGGQQGSPKH GPHSGAPKSL PREEPELRPR PPRPLDSHLA
460 470 480 490 500
INGSANRQSK SESDYSDGDN DSINSTSNSN DTINCSSESS SRDSLREQTL
510 520 530 540 550
SKQTYHKEAR NSWDSPAFSN DVIRKRHYRI GLNLFNKKPE KGVQYLIERG
560 570 580 590 600
FVPDTPVGVA HFLLQRKGLS RQMIGEFLGN RQKQFNRDVL DCVVDEMDFS
610 620 630 640 650
TMELDEALRK FQAHIRVQGE AQKVERLIEA FSQRYCICNP GVVRQFRNPD
660 670 680 690 700
TIFILAFAII LLNTDMYSPN VKPERKMKLE DFIKNLRGVD DGEDIPREML
710 720 730 740 750
MGIYERIRKR ELKTNEDHVS QVQKVEKLIV GKKPIGSLHP GLGCVLSLPH
760 770 780 790 800
RRLVCYCRLF EVPDPNKPQK LGLHQREIFL FNDLLVVTKI FQKKKNSVTY
810 820 830 840 850
SFRQSFSLYG MQVLLFENQY YPNGIRLTSS VPGADIKVLI NFNAPNPQDR
860 870 880 890 900
KKFTDDLRES IAEVQEMEKH RIESELEKQK GVVRPSMSQC SSLKKESGNG
910 920 930 940 950
TLSRACLDDS YASGEGLKRS ALSSSLRDLS EAGKRGRRSS AGSLESNVEF
960
QPFEPLQPSV LCS
Length:963
Mass (Da):108,314
Last modified:August 16, 2004 - v1
Checksum:i5B31F9918F9CFF11
GO
Isoform 2 (identifier: Q6DN90-2) [UniParc]FASTAAdd to basket

Also known as: BRAG2a

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.

Note: No experimental confirmation available.

Show »
Length:841
Mass (Da):94,914
Checksum:i504A8DDC71EB8B71
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti934 – 9363KRG → VHH (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti640 – 6401P → S.
Corresponds to variant rs35319679 [ dbSNP | Ensembl ].
VAR_051927
Natural varianti882 – 8821V → I.
Corresponds to variant rs17541405 [ dbSNP | Ensembl ].
VAR_027004

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 122122Missing in isoform 2. 2 PublicationsVSP_019758Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY653734 mRNA. Translation: AAT72063.1.
AB018306 mRNA. Translation: BAA34483.2.
BC010267 mRNA. Translation: AAH10267.1.
CCDSiCCDS33703.1. [Q6DN90-1]
RefSeqiNP_001127854.1. NM_001134382.2.
NP_055684.3. NM_014869.6. [Q6DN90-1]
UniGeneiHs.475506.

Genome annotation databases

EnsembliENST00000273221; ENSP00000273221; ENSG00000144711. [Q6DN90-1]
GeneIDi9922.
KEGGihsa:9922.
UCSCiuc003bxt.3. human. [Q6DN90-1]

Polymorphism databases

DMDMi74748429.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY653734 mRNA. Translation: AAT72063.1.
AB018306 mRNA. Translation: BAA34483.2.
BC010267 mRNA. Translation: AAH10267.1.
CCDSiCCDS33703.1. [Q6DN90-1]
RefSeqiNP_001127854.1. NM_001134382.2.
NP_055684.3. NM_014869.6. [Q6DN90-1]
UniGeneiHs.475506.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QWMX-ray2.39A743-880[»]
4C0AX-ray3.30A/B/E/F512-885[»]
ProteinModelPortaliQ6DN90.
SMRiQ6DN90. Positions 515-880.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115250. 9 interactions.
IntActiQ6DN90. 6 interactions.
STRINGi9606.ENSP00000273221.

Polymorphism databases

DMDMi74748429.

Proteomic databases

MaxQBiQ6DN90.
PaxDbiQ6DN90.
PRIDEiQ6DN90.

Protocols and materials databases

DNASUi9922.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273221; ENSP00000273221; ENSG00000144711. [Q6DN90-1]
GeneIDi9922.
KEGGihsa:9922.
UCSCiuc003bxt.3. human. [Q6DN90-1]

Organism-specific databases

CTDi9922.
GeneCardsiGC03M012938.
HGNCiHGNC:29112. IQSEC1.
HPAiHPA038143.
HPA038144.
MIMi610166. gene.
neXtProtiNX_Q6DN90.
PharmGKBiPA128394566.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5307.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000113099.
HOVERGENiHBG056324.
InParanoidiQ6DN90.
KOiK12495.
PhylomeDBiQ6DN90.
TreeFamiTF323811.

Miscellaneous databases

ChiTaRSiIQSEC1. human.
GeneWikiiIQSEC1.
GenomeRNAii9922.
NextBioi37432.
PROiQ6DN90.
SOURCEiSearch...

Gene expression databases

BgeeiQ6DN90.
CleanExiHS_IQSEC1.
GenevestigatoriQ6DN90.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000048. IQ_motif_EF-hand-BS.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamiPF01369. Sec7. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48425. SSF48425. 1 hit.
PROSITEiPS50096. IQ. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins."
    Dunphy J.L., Moravec R., Ly K., Lasell T.K., Melancon P., Casanova J.E.
    Curr. Biol. 16:315-320(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
  2. "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 5:277-286(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
    Tissue: Brain.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-936 (ISOFORM 2).
    Tissue: Placenta.
  4. "ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-ribosylation factor 6."
    Someya A., Sata M., Takeda K., Pacheco-Rodriguez G., Ferrans V.J., Moss J., Vaughan M.
    Proc. Natl. Acad. Sci. U.S.A. 98:2413-2418(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH ARF6.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  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(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180 AND SER-512, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180; SER-253; SER-512; TYR-911; SER-924 AND SER-925, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  10. "Crystal Structure of GEP100, the plextrin homology domain of IQ motif and SEC7 domain-containing protein 1 isoform a."
    Structural genomics consortium (SGC)
    Submitted (JAN-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 743-880.
  11. "Integrated conformational and lipid-sensing regulation of endosomal ArfGEF BRAG2."
    Aizel K., Biou V., Navaza J., Duarte L.V., Campanacci V., Cherfils J., Zeghouf M.
    PLoS Biol. 11:E1001652-E1001652(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 512-885 OF MUTANT LYS-620 IN COMPLEX WITH ARF1, INTERACTION WITH ARF1, FUNCTION, MUTAGENESIS OF GLU-620, DOMAIN.

Entry informationi

Entry nameiIQEC1_HUMAN
AccessioniPrimary (citable) accession number: Q6DN90
Secondary accession number(s): O94863, Q96D85
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: August 16, 2004
Last modified: April 1, 2015
This is version 106 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.