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Protein

Brefeldin A-inhibited guanine nucleotide-exchange protein 1

Gene

ARFGEF1

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

Functioni

Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturaion of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competetive RhoA binding. The function in the nucleus remains to be determined.5 Publications

Enzyme regulationi

Inhibited by brefeldin A.

GO - Molecular functioni

  • ARF guanyl-nucleotide exchange factor activity Source: GO_Central
  • guanyl-nucleotide exchange factor activity Source: UniProtKB
  • myosin binding Source: UniProtKB
  • protein kinase A regulatory subunit binding Source: UniProtKB

GO - Biological processi

  • endomembrane system organization Source: UniProtKB
  • exocytosis Source: ProtInc
  • Golgi organization Source: UniProtKB
  • negative regulation of actin filament polymerization Source: UniProtKB
  • negative regulation of GTPase activity Source: UniProtKB
  • neuron projection development Source: Ensembl
  • positive regulation of protein glycosylation in Golgi Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: Ensembl
  • positive regulation of wound healing Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of ARF protein signal transduction Source: InterPro
  • regulation of establishment of cell polarity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000066777-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Brefeldin A-inhibited guanine nucleotide-exchange protein 1
Short name:
Brefeldin A-inhibited GEP 1
Alternative name(s):
ADP-ribosylation factor guanine nucleotide-exchange factor 1
p200 ARF guanine nucleotide exchange factor
p200 ARF-GEP1
Gene namesi
Name:ARFGEF1
Synonyms:ARFGEP1, BIG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:15772. ARFGEF1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: UniProtKB
  • Golgi apparatus Source: HPA
  • Golgi membrane Source: UniProtKB
  • nuclear matrix Source: UniProtKB-SubCell
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: HPA
  • perinuclear region of cytoplasm Source: UniProtKB
  • small nuclear ribonucleoprotein complex Source: UniProtKB
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi221E → K: No effect on self-association. 1 Publication1
Mutagenesisi712 – 714KPK → AAA: Inhibits nuclear localization. 1 Publication3
Mutagenesisi883S → A: Abolishes cAMP-induced nuclear localization. 1 Publication1
Mutagenesisi883S → D: No effect on cAMP-induced nuclear localization. 1 Publication1

Organism-specific databases

DisGeNETi10565.
OpenTargetsiENSG00000066777.
PharmGKBiPA134908197.

Polymorphism and mutation databases

BioMutaiARFGEF1.
DMDMi116241267.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001202071 – 1849Brefeldin A-inhibited guanine nucleotide-exchange protein 1Add BLAST1849

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphoserineCombined sources1
Modified residuei234PhosphoserineBy similarity1
Modified residuei243PhosphoserineBy similarity1
Modified residuei269PhosphothreonineBy similarity1
Modified residuei286PhosphoserineBy similarity1
Modified residuei289PhosphoserineBy similarity1
Modified residuei290PhosphoserineBy similarity1
Modified residuei396PhosphoserineBy similarity1
Modified residuei397PhosphoserineCombined sources1
Modified residuei410PhosphoserineCombined sources1
Modified residuei664PhosphoserineBy similarity1
Modified residuei667PhosphoserineBy similarity1
Modified residuei681PhosphothreonineBy similarity1
Modified residuei1079PhosphoserineCombined sources1
Modified residuei1566PhosphoserineBy similarity1
Modified residuei1569PhosphoserineCombined sources1
Modified residuei1593PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated. In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y6D6.
MaxQBiQ9Y6D6.
PaxDbiQ9Y6D6.
PeptideAtlasiQ9Y6D6.
PRIDEiQ9Y6D6.

PTM databases

iPTMnetiQ9Y6D6.
PhosphoSitePlusiQ9Y6D6.

Expressioni

Tissue specificityi

Expressed in placenta, lung, heart, brain, kidney and pancreas.

Gene expression databases

BgeeiENSG00000066777.
CleanExiHS_ARFGEF1.
ExpressionAtlasiQ9Y6D6. baseline and differential.
GenevisibleiQ9Y6D6. HS.

Organism-specific databases

HPAiHPA023399.
HPA023822.

Interactioni

Subunit structurei

Homodimer (PubMed:17640864). Interacts with ARFGEF2/BIG2; both proteins are probably part of the same or very similar macromolecular complexes (PubMed:10716990). Interacts with FKBP2 (PubMed:12606707). Interacts with MYO9B (PubMed:15644318). Interacts with PRKAR1A and PRKAR2A (PubMed:12571360). Interacts with PPP1CC (PubMed:17360629). Interacts with NCL, FBL, NUP62 and U3 small nucleolar RNA (PubMed:14973189, PubMed:18292223). Interacts with DPY30 (PubMed:19651892). Interacts with PDE3A (PubMed:19332778). Interacts with KANK1 (PubMed:22084092). Interacts with TBC1D22A and TBC1D22B (PubMed:23572552).12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARFGEF2Q9Y6D53EBI-1044254,EBI-2837511
KIF21AQ7Z4S6-24EBI-1044254,EBI-6251716
MYCBPQ994173EBI-1044254,EBI-716185
MYO9BQ13459-22EBI-1044254,EBI-6251250

GO - Molecular functioni

  • myosin binding Source: UniProtKB
  • protein kinase A regulatory subunit binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115816. 25 interactors.
DIPiDIP-29748N.
IntActiQ9Y6D6. 11 interactors.
MINTiMINT-1728435.
STRINGi9606.ENSP00000262215.

Structurei

Secondary structure

11849
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi7 – 21Combined sources15
Helixi23 – 25Combined sources3
Helixi28 – 30Combined sources3
Helixi31 – 48Combined sources18
Helixi77 – 80Combined sources4
Helixi81 – 88Combined sources8
Helixi93 – 108Combined sources16
Helixi126 – 135Combined sources10
Helixi145 – 160Combined sources16
Helixi168 – 184Combined sources17
Helixi188 – 224Combined sources37
Helixi698 – 711Combined sources14
Helixi713 – 722Combined sources10
Helixi730 – 739Combined sources10
Helixi745 – 752Combined sources8
Helixi757 – 768Combined sources12
Helixi777 – 786Combined sources10
Helixi794 – 810Combined sources17
Helixi821 – 838Combined sources18
Helixi849 – 855Combined sources7
Beta strandi861 – 864Combined sources4
Helixi867 – 879Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LTLX-ray2.20A/B691-889[»]
5EE5X-ray2.28A1-229[»]
5J5CX-ray3.40B1-224[»]
ProteinModelPortaliQ9Y6D6.
SMRiQ9Y6D6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y6D6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini709 – 840SEC7PROSITE-ProRule annotationAdd BLAST132

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 224DCB; DCB:DCB domain and DCB:HUS domain interactionAdd BLAST223
Regioni557 – 577HUS; DCB:HUS domain interactionAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi711 – 715Nuclear localization signal (NLS)5

Sequence similaritiesi

Contains 1 SEC7 domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0929. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000181045.
HOVERGENiHBG004846.
InParanoidiQ9Y6D6.
KOiK18442.
OMAiWATHRID.
OrthoDBiEOG091G00F0.
PhylomeDBiQ9Y6D6.
TreeFamiTF300714.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
1.25.10.10. 4 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR032629. DCB_dom.
IPR023394. Sec7_alpha_orthog.
IPR015403. Sec7_C.
IPR000904. Sec7_dom.
IPR032691. Sec7_N.
[Graphical view]
PfamiPF16213. DCB. 1 hit.
PF09324. DUF1981. 1 hit.
PF01369. Sec7. 1 hit.
PF12783. Sec7_N. 1 hit.
[Graphical view]
SMARTiSM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
SSF48425. SSF48425. 1 hit.
PROSITEiPS50190. SEC7. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y6D6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MYEGKKTKNM FLTRALEKIL ADKEVKKAHH SQLRKACEVA LEEIKAETEK
60 70 80 90 100
QSPPHGEAKA GSSTLPPVKS KTNFIEADKY FLPFELACQS KCPRIVSTSL
110 120 130 140 150
DCLQKLIAYG HLTGNAPDST TPGKKLIDRI IETICGCFQG PQTDEGVQLQ
160 170 180 190 200
IIKALLTAVT SQHIEIHEGT VLQAVRTCYN IYLASKNLIN QTTAKATLTQ
210 220 230 240 250
MLNVIFARME NQALQEAKQM EKERHRQHHH LLQSPVSHHE PESPQLRYLP
260 270 280 290 300
PQTVDHISQE HEGDLDLHTN DVDKSLQDDT EPENGSDISS AENEQTEADQ
310 320 330 340 350
ATAAETLSKN EVLYDGENHD CEEKPQDIVQ NIVEEMVNIV VGDMGEGTTI
360 370 380 390 400
NASADGNIGT IEDGSDSENI QANGIPGTPI SVAYTPSLPD DRLSVSSNDT
410 420 430 440 450
QESGNSSGPS PGAKFSHILQ KDAFLVFRSL CKLSMKPLSD GPPDPKSHEL
460 470 480 490 500
RSKILSLQLL LSILQNAGPI FRTNEMFINA IKQYLCVALS KNGVSSVPEV
510 520 530 540 550
FELSLSIFLT LLSNFKTHLK MQIEVFFKEI FLYILETSTS SFDHKWMVIQ
560 570 580 590 600
TLTRICADAQ SVVDIYVNYD CDLNAANIFE RLVNDLSKIA QGRGSQELGM
610 620 630 640 650
SNVQELSLRK KGLECLVSIL KCMVEWSKDQ YVNPNSQTTL GQEKPSEQEM
660 670 680 690 700
SEIKHPETIN RYGSLNSLES TSSSGIGSYS TQMSGTDNPE QFEVLKQQKE
710 720 730 740 750
IIEQGIDLFN KKPKRGIQYL QEQGMLGTTP EDIAQFLHQE ERLDSTQVGE
760 770 780 790 800
FLGDNDKFNK EVMYAYVDQH DFSGKDFVSA LRMFLEGFRL PGEAQKIDRL
810 820 830 840 850
MEKFAARYLE CNQGQTLFAS ADTAYVLAYS IIMLTTDLHS PQVKNKMTKE
860 870 880 890 900
QYIKMNRGIN DSKDLPEEYL SAIYNEIAGK KISMKETKEL TIPTKSSKQN
910 920 930 940 950
VASEKQRRLL YNLEMEQMAK TAKALMEAVS HVQAPFTSAT HLEHVRPMFK
960 970 980 990 1000
LAWTPFLAAF SVGLQDCDDT EVASLCLEGI RCAIRIACIF SIQLERDAYV
1010 1020 1030 1040 1050
QALARFTLLT VSSGITEMKQ KNIDTIKTLI TVAHTDGNYL GNSWHEILKC
1060 1070 1080 1090 1100
ISQLELAQLI GTGVKPRYIS GTVRGREGSL TGTKDQAPDE FVGLGLVGGN
1110 1120 1130 1140 1150
VDWKQIASIQ ESIGETSSQS VVVAVDRIFT GSTRLDGNAI VDFVRWLCAV
1160 1170 1180 1190 1200
SMDELLSTTH PRMFSLQKIV EISYYNMGRI RLQWSRIWEV IGDHFNKVGC
1210 1220 1230 1240 1250
NPNEDVAIFA VDSLRQLSMK FLEKGELANF RFQKDFLRPF EHIMKRNRSP
1260 1270 1280 1290 1300
TIRDMVVRCI AQMVNSQAAN IRSGWKNIFS VFHLAASDQD ESIVELAFQT
1310 1320 1330 1340 1350
TGHIVTLVFE KHFPATIDSF QDAVKCLSEF ACNAAFPDTS MEAIRLIRHC
1360 1370 1380 1390 1400
AKYVSDRPQA FKEYTSDDMN VAPEDRVWVR GWFPILFELS CIINRCKLDV
1410 1420 1430 1440 1450
RTRGLTVMFE IMKTYGHTYE KHWWQDLFRI VFRIFDNMKL PEQQTEKAEW
1460 1470 1480 1490 1500
MTTTCNHALY AICDVFTQYL EVLSDVLLDD IFAQLYWCVQ QDNEQLARSG
1510 1520 1530 1540 1550
TNCLENVVIL NGEKFTLEIW DKTCNCTLDI FKTTIPHALL TWRPNSGETA
1560 1570 1580 1590 1600
PPPPSPVSEK PLDTISQKSV DIHDSIQPRS VDNRPQAPLV SASAVNEEVS
1610 1620 1630 1640 1650
KIKSTAKFPE QKLFAALLIK CVVQLELIQT IDNIVFFPAT SKKEDAENLA
1660 1670 1680 1690 1700
AAQRDAVDFD VRVDTQDQGM YRFLTSQQLF KLLDCLLESH RFAKAFNSNN
1710 1720 1730 1740 1750
EQRTALWKAG FKGKSKPNLL KQETSSLACG LRILFRMYMD ESRVSAWEEV
1760 1770 1780 1790 1800
QQRLLNVCSE ALSYFLTLTS ESHREAWTNL LLLFLTKVLK ISDNRFKAHA
1810 1820 1830 1840
SFYYPLLCEI MQFDLIPELR AVLRRFFLRI GVVFQISQPP EQELGINKQ
Length:1,849
Mass (Da):208,767
Last modified:October 17, 2006 - v2
Checksum:i1EB2547F28F63BCA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti233Q → P in AAD38427 (PubMed:10212200).Curated1
Sequence conflicti620L → S in AAD38427 (PubMed:10212200).Curated1
Sequence conflicti1055E → K in AAD38427 (PubMed:10212200).Curated1
Sequence conflicti1590V → A in BAA91912 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028749273D → Y.Corresponds to variant rs4321984dbSNPEnsembl.1
Natural variantiVAR_036155316G → E in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084520 mRNA. Translation: AAD38427.1.
AF111162 mRNA. Translation: AAD43651.1.
AK001788 mRNA. Translation: BAA91912.1.
AL117446 mRNA. Translation: CAB55931.1.
CCDSiCCDS6199.1.
PIRiT17241.
RefSeqiNP_006412.2. NM_006421.4.
XP_005251191.1. XM_005251134.4.
UniGeneiHs.656902.

Genome annotation databases

EnsembliENST00000262215; ENSP00000262215; ENSG00000066777.
GeneIDi10565.
KEGGihsa:10565.
UCSCiuc003xxo.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084520 mRNA. Translation: AAD38427.1.
AF111162 mRNA. Translation: AAD43651.1.
AK001788 mRNA. Translation: BAA91912.1.
AL117446 mRNA. Translation: CAB55931.1.
CCDSiCCDS6199.1.
PIRiT17241.
RefSeqiNP_006412.2. NM_006421.4.
XP_005251191.1. XM_005251134.4.
UniGeneiHs.656902.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LTLX-ray2.20A/B691-889[»]
5EE5X-ray2.28A1-229[»]
5J5CX-ray3.40B1-224[»]
ProteinModelPortaliQ9Y6D6.
SMRiQ9Y6D6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115816. 25 interactors.
DIPiDIP-29748N.
IntActiQ9Y6D6. 11 interactors.
MINTiMINT-1728435.
STRINGi9606.ENSP00000262215.

PTM databases

iPTMnetiQ9Y6D6.
PhosphoSitePlusiQ9Y6D6.

Polymorphism and mutation databases

BioMutaiARFGEF1.
DMDMi116241267.

Proteomic databases

EPDiQ9Y6D6.
MaxQBiQ9Y6D6.
PaxDbiQ9Y6D6.
PeptideAtlasiQ9Y6D6.
PRIDEiQ9Y6D6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262215; ENSP00000262215; ENSG00000066777.
GeneIDi10565.
KEGGihsa:10565.
UCSCiuc003xxo.2. human.

Organism-specific databases

CTDi10565.
DisGeNETi10565.
GeneCardsiARFGEF1.
HGNCiHGNC:15772. ARFGEF1.
HPAiHPA023399.
HPA023822.
MIMi604141. gene.
neXtProtiNX_Q9Y6D6.
OpenTargetsiENSG00000066777.
PharmGKBiPA134908197.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0929. Eukaryota.
COG5307. LUCA.
GeneTreeiENSGT00760000119036.
HOGENOMiHOG000181045.
HOVERGENiHBG004846.
InParanoidiQ9Y6D6.
KOiK18442.
OMAiWATHRID.
OrthoDBiEOG091G00F0.
PhylomeDBiQ9Y6D6.
TreeFamiTF300714.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000066777-MONOMER.

Miscellaneous databases

ChiTaRSiARFGEF1. human.
EvolutionaryTraceiQ9Y6D6.
GeneWikiiARFGEF1.
GenomeRNAii10565.
PROiQ9Y6D6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000066777.
CleanExiHS_ARFGEF1.
ExpressionAtlasiQ9Y6D6. baseline and differential.
GenevisibleiQ9Y6D6. HS.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
1.25.10.10. 4 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR032629. DCB_dom.
IPR023394. Sec7_alpha_orthog.
IPR015403. Sec7_C.
IPR000904. Sec7_dom.
IPR032691. Sec7_N.
[Graphical view]
PfamiPF16213. DCB. 1 hit.
PF09324. DUF1981. 1 hit.
PF01369. Sec7. 1 hit.
PF12783. Sec7_N. 1 hit.
[Graphical view]
SMARTiSM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
SSF48425. SSF48425. 1 hit.
PROSITEiPS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBIG1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6D6
Secondary accession number(s): Q9NV46, Q9UFV2, Q9UNL0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 151 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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

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.