BIG3_HUMAN
ID BIG3_HUMAN Reviewed; 2177 AA.
AC Q5TH69; C5NM88; Q76MU8; Q8N4Y4; Q96CH9; Q96P46; Q9ULH6;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Brefeldin A-inhibited guanine nucleotide-exchange protein 3 {ECO:0000305};
DE AltName: Full=ARFGEF family member 3 {ECO:0000312|HGNC:HGNC:21213};
GN Name=ARFGEF3 {ECO:0000312|HGNC:HGNC:21213};
GN Synonyms=BIG3, C6orf92, KIAA1244;
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], FUNCTION, INTERACTION WITH PHB2, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Mammary cancer {ECO:0000312|EMBL:BAH83562.1};
RX PubMed=19496786; DOI=10.1111/j.1349-7006.2009.01209.x;
RA Kim J.W., Akiyama M., Park J.H., Lin M.L., Shimo A., Ueki T., Daigo Y.,
RA Tsunoda T., Nishidate T., Nakamura Y., Katagiri T.;
RT "Activation of an estrogen/estrogen receptor signaling by BIG3 through its
RT inhibitory effect on nuclear transport of PHB2/REA in breast cancer.";
RL Cancer Sci. 100:1468-1478(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 306-2177.
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 408-2177.
RA Hong W.;
RT "KIAA1244 as a novel distantly related member (BIG3) of the BIG1/Sec7p
RT subfamily of ARF GEFs.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1588-2177.
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1991, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Participates in the regulation of systemic glucose
CC homeostasis, where it negatively regulates insulin granule biogenesis
CC in pancreatic islet beta cells (By similarity). Also regulates glucagon
CC granule production in pancreatic alpha cells (By similarity). Inhibits
CC nuclear translocation of the transcriptional coregulator PHB2 and may
CC enhance estrogen receptor alpha (ESR1) transcriptional activity in
CC breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8,
CC ECO:0000269|PubMed:19496786}.
CC -!- SUBUNIT: Interacts with PHB2. {ECO:0000269|PubMed:19496786}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19496786}.
CC Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:Q3UGY8}.
CC Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000305}; Single-
CC pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in breast cancer cell lines. Not
CC expressed in normal tissues such as duct, mammary gland, lung, heart,
CC liver, kidnay, bone marrow. {ECO:0000269|PubMed:19496786}.
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DR EMBL; AB252196; BAH83562.1; -; mRNA.
DR EMBL; AL031433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391240; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB033070; BAA86558.2; -; mRNA.
DR EMBL; AF413080; AAL04174.1; -; mRNA.
DR EMBL; BC014227; AAH14227.2; -; mRNA.
DR EMBL; BC033191; AAH33191.1; -; mRNA.
DR CCDS; CCDS5189.2; -.
DR RefSeq; NP_065073.3; NM_020340.4.
DR AlphaFoldDB; Q5TH69; -.
DR BioGRID; 121457; 74.
DR IntAct; Q5TH69; 16.
DR MINT; Q5TH69; -.
DR STRING; 9606.ENSP00000251691; -.
DR GlyGen; Q5TH69; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5TH69; -.
DR PhosphoSitePlus; Q5TH69; -.
DR BioMuta; ARFGEF3; -.
DR DMDM; 147742985; -.
DR EPD; Q5TH69; -.
DR jPOST; Q5TH69; -.
DR MassIVE; Q5TH69; -.
DR MaxQB; Q5TH69; -.
DR PaxDb; Q5TH69; -.
DR PeptideAtlas; Q5TH69; -.
DR PRIDE; Q5TH69; -.
DR ProteomicsDB; 65144; -.
DR Antibodypedia; 52580; 8 antibodies from 6 providers.
DR DNASU; 57221; -.
DR Ensembl; ENST00000251691.5; ENSP00000251691.4; ENSG00000112379.9.
DR GeneID; 57221; -.
DR KEGG; hsa:57221; -.
DR MANE-Select; ENST00000251691.5; ENSP00000251691.4; NM_020340.5; NP_065073.3.
DR UCSC; uc003qhu.4; human.
DR CTD; 57221; -.
DR DisGeNET; 57221; -.
DR GeneCards; ARFGEF3; -.
DR HGNC; HGNC:21213; ARFGEF3.
DR HPA; ENSG00000112379; Tissue enhanced (brain, salivary gland).
DR MIM; 617411; gene.
DR neXtProt; NX_Q5TH69; -.
DR OpenTargets; ENSG00000112379; -.
DR PharmGKB; PA134888863; -.
DR VEuPathDB; HostDB:ENSG00000112379; -.
DR eggNOG; KOG1846; Eukaryota.
DR GeneTree; ENSGT00530000064150; -.
DR HOGENOM; CLU_000867_1_0_1; -.
DR InParanoid; Q5TH69; -.
DR OMA; AGYYEQV; -.
DR OrthoDB; 40522at2759; -.
DR PhylomeDB; Q5TH69; -.
DR TreeFam; TF300714; -.
DR PathwayCommons; Q5TH69; -.
DR SignaLink; Q5TH69; -.
DR BioGRID-ORCS; 57221; 7 hits in 1074 CRISPR screens.
DR ChiTaRS; ARFGEF3; human.
DR GenomeRNAi; 57221; -.
DR Pharos; Q5TH69; Tdark.
DR PRO; PR:Q5TH69; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q5TH69; protein.
DR Bgee; ENSG00000112379; Expressed in parotid gland and 163 other tissues.
DR Genevisible; Q5TH69; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR CDD; cd00171; Sec7; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032629; DCB_dom.
DR InterPro; IPR015403; Sec7_C.
DR InterPro; IPR000904; Sec7_dom.
DR Pfam; PF16213; DCB; 1.
DR Pfam; PF09324; DUF1981; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoplasmic vesicle; Guanine-nucleotide releasing factor;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..2177
FT /note="Brefeldin A-inhibited guanine nucleotide-exchange
FT protein 3"
FT /id="PRO_0000286671"
FT TRANSMEM 1492..1512
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 583..796
FT /note="SEC7"
FT REGION 282..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 617..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1031..1076
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1848..1877
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1946..2004
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2033..2064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2082..2103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..529
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1031..1048
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1959..1973
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2033..2055
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 636
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 1049
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 1991
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2079
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 2081
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 2095
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 2101
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT MOD_RES 2103
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGY8"
FT VARIANT 413
FT /note="E -> D (in dbSNP:rs9376338)"
FT /id="VAR_051925"
FT VARIANT 689
FT /note="S -> A (in dbSNP:rs7764091)"
FT /id="VAR_032154"
FT VARIANT 1571
FT /note="A -> T (in dbSNP:rs3736706)"
FT /id="VAR_032155"
FT VARIANT 2031
FT /note="K -> R (in dbSNP:rs35964895)"
FT /id="VAR_032156"
FT CONFLICT 1876
FT /note="Missing (in Ref. 6; AAH14227/AAH33191)"
FT /evidence="ECO:0000305"
FT CONFLICT 1883
FT /note="R -> L (in Ref. 6; AAH14227/AAH33191)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2177 AA; 240652 MW; 6F48EDB5BFF37454 CRC64;
MEEILRKLQK EASGSKYKAI KESCTWALET LGGLDTIVKI PPHVLREKCL LPLQLALESK
NVKLAQHALA GMQKLLSEER FVSMETDSDE KQLLNQILNA VKVTPSLNED LQVEVMKVLL
CITYTPTFDL NGSAVLKIAE VCIETYISSC HQRSINTAVR ATLSQMLSDL TLQLRQRQEN
TIIENPDVPQ DFGNQGSTVE SLCDDVVSVL TVLCEKLQAA INDSQQLQLL YLECILSVLS
SSSSSMHLHR RFTDLIWKNL CPALIVILGN PIHDKTITSA HTSSTSTSLE SDSASPGVSD
HGRGSGCSCT APALSGPVAR TIYYIAAELV RLVGSVDSMK PVLQSLYHRV LLYPPPQHRV
EAIKIMKEIL GSPQRLCDLA GPSSTESESR KRSISKRKSH LDLLKLIMDG MTEACIKGGI
EACYAAVSCV CTLLGALDEL SQGKGLSEGQ VQLLLLRLEE LKDGAEWSRD SMEINEADFR
WQRRVLSSEH TPWESGNERS LDISISVTTD TGQTTLEGEL GQTTPEDHSG NHKNSLKSPA
IPEGKETLSK VLETEAVDQP DVVQRSHTVP YPDITNFLSV DCRTRSYGSR YSESNFSVDD
QDLSRTEFDS CDQYSMAAEK DSGRSDVSDI GSDNCSLADE EQTPRDCLGH RSLRTAALSL
KLLKNQEADQ HSARLFIQSL EGLLPRLLSL SNVEEVDTAL QNFASTFCSG MMHSPGFDGN
SSLSFQMLMN ADSLYTAAHC ALLLNLKLSH GDYYRKRPTL APGVMKDFMK QVQTSGVLMV
FSQAWIEELY HQVLDRNMLG EAGYWGSPED NSLPLITMLT DIDGLESSAI GGQLMASAAT
ESPFAQSRRI DDSTVAGVAF ARYILVGCWK NLIDTLSTPL TGRMAGSSKG LAFILGAEGI
KEQNQKERDA ICMSLDGLRK AARLSCALGV AANCASALAQ MAAASCVQEE KEEREAQEPS
DAITQVKLKV EQKLEQIGKV QGVWLHTAHV LCMEAILSVG LEMGSHNPDC WPHVFRVCEY
VGTLEHNHFS DGASQPPLTI SQPQKATGSA GLLGDPECEG SPPEHSPEQG RSLSTAPVVQ
PLSIQDLVRE GSRGRASDFR GGSLMSGSSA AKVVLTLSTQ ADRLFEDATD KLNLMALGGF
LYQLKKASQS QLFHSVTDTV DYSLAMPGEV KSTQDRKSAL HLFRLGNAML RIVRSKARPL
LHVMRCWSLV APHLVEAACH KERHVSQKAV SFIHDILTEV LTDWNEPPHF HFNEALFRPF
ERIMQLELCD EDVQDQVVTS IGELVEVCST QIQSGWRPLF SALETVHGGN KSEMKEYLVG
DYSMGKGQAP VFDVFEAFLN TDNIQVFANA ATSYIMCLMK FVKGLGEVDC KEIGDCAPAP
GAPSTDLCLP ALDYLRRCSQ LLAKIYKMPL KPIFLSGRLA GLPRRLQEQS ASSEDGIESV
LSDFDDDTGL IEVWIILLEQ LTAAVSNCPR QHQPPTLDLL FELLRDVTKT PGPGFGIYAV
VHLLLPVMSV WLRRSHKDHS YWDMASANFK HAIGLSCELV VEHIQSFLHS DIRYESMINT
MLKDLFELLV ACVAKPTETI SRVGCSCIRY VLVTAGPVFT EEMWRLACCA LQDAFSATLK
PVKDLLGCFH SGTESFSGEG CQVRVAAPSS SPSAEAEYWR IRAMAQQVFM LDTQCSPKTP
NNFDHAQSCQ LIIELPPDEK PNGHTKKSVS FREIVVSLLS HQVLLQNLYD ILLEEFVKGP
SPGEEKTIQV PEAKLAGFLR YISMQNLAVI FDLLLDSYRT AREFDTSPGL KCLLKKVSGI
GGAANLYRQS AMSFNIYFHA LVCAVLTNQE TITAEQVKKV LFEDDERSTD SSQQCSSEDE
DIFEETAQVS PPRGKEKRQW RARMPLLSVQ PVSNADWVWL VKRLHKLCME LCNNYIQMHL
DLENCMEEPP IFKGDPFFIL PSFQSESSTP STGGFSGKET PSEDDRSQSR EHMGESLSLK
AGGGDLLLPP SPKVEKKDPS RKKEWWENAG NKIYTMAADK TISKLMTEYK KRKQQHNLSA
FPKEVKVEKK GEPLGPRGQD SPLLQRPQHL MDQGQMRHSF SAGPELLRQD KRPRSGSTGS
SLSVSVRDAE AQIQAWTNMV LTVLNQIQIL PDQTFTALQP AVFPCISQLT CHVTDIRVRQ
AVREWLGRVG RVYDIIV
