DEN4B_HUMAN
ID DEN4B_HUMAN Reviewed; 1496 AA.
AC O75064; Q5T4K0;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 4.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=DENN domain-containing protein 4B;
GN Name=DENND4B; Synonyms=KIAA0476;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION.
RX PubMed=12906859; DOI=10.1016/s0888-7543(03)00103-4;
RA Semova N., Kapanadze B., Corcoran M., Kutsenko A., Baranova A., Semov A.;
RT "Molecular cloning, structural analysis, and expression of a human IRLB,
RT MYC promoter-binding protein: new DENN domain-containing protein family
RT emerges.";
RL Genomics 82:343-354(2003).
RN [5]
RP FUNCTION AS GUANYL-NUCLEOTIDE EXCHANGE FACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=20937701; DOI=10.1083/jcb.201008051;
RA Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A.;
RT "Family-wide characterization of the DENN domain Rab GDP-GTP exchange
RT factors.";
RL J. Cell Biol. 191:367-381(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-953 AND SER-1092, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate
CC RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-
CC bound Rab proteins into their active GTP-bound form.
CC {ECO:0000269|PubMed:20937701}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000269|PubMed:20937701}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32321.3; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=EAW53268.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AB007945; BAA32321.3; ALT_INIT; mRNA.
DR EMBL; AL358472; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53268.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS44228.1; -.
DR PIR; T00257; T00257.
DR RefSeq; NP_055671.2; NM_014856.2.
DR RefSeq; XP_005245736.1; XM_005245679.2.
DR AlphaFoldDB; O75064; -.
DR SMR; O75064; -.
DR BioGRID; 115238; 15.
DR IntAct; O75064; 5.
DR STRING; 9606.ENSP00000354597; -.
DR iPTMnet; O75064; -.
DR PhosphoSitePlus; O75064; -.
DR BioMuta; DENND4B; -.
DR EPD; O75064; -.
DR jPOST; O75064; -.
DR MassIVE; O75064; -.
DR MaxQB; O75064; -.
DR PaxDb; O75064; -.
DR PeptideAtlas; O75064; -.
DR PRIDE; O75064; -.
DR ProteomicsDB; 49735; -.
DR Antibodypedia; 50670; 28 antibodies from 8 providers.
DR DNASU; 9909; -.
DR Ensembl; ENST00000361217.9; ENSP00000354597.4; ENSG00000198837.10.
DR GeneID; 9909; -.
DR KEGG; hsa:9909; -.
DR MANE-Select; ENST00000361217.9; ENSP00000354597.4; NM_014856.3; NP_055671.2.
DR UCSC; uc001fdd.2; human.
DR CTD; 9909; -.
DR DisGeNET; 9909; -.
DR GeneCards; DENND4B; -.
DR HGNC; HGNC:29044; DENND4B.
DR HPA; ENSG00000198837; Low tissue specificity.
DR MIM; 619843; gene.
DR neXtProt; NX_O75064; -.
DR OpenTargets; ENSG00000198837; -.
DR PharmGKB; PA142671629; -.
DR VEuPathDB; HostDB:ENSG00000198837; -.
DR eggNOG; KOG2127; Eukaryota.
DR GeneTree; ENSGT00940000160472; -.
DR InParanoid; O75064; -.
DR OMA; VVWPGPI; -.
DR OrthoDB; 75304at2759; -.
DR PhylomeDB; O75064; -.
DR TreeFam; TF313237; -.
DR PathwayCommons; O75064; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; O75064; -.
DR BioGRID-ORCS; 9909; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; DENND4B; human.
DR GenomeRNAi; 9909; -.
DR Pharos; O75064; Tbio.
DR PRO; PR:O75064; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75064; protein.
DR Bgee; ENSG00000198837; Expressed in granulocyte and 204 other tissues.
DR ExpressionAtlas; O75064; baseline and differential.
DR Genevisible; O75064; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; IDA:FlyBase.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.40.50.11500; -; 1.
DR InterPro; IPR001194; cDENN_dom.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR043153; DENN_C.
DR InterPro; IPR023341; MABP.
DR InterPro; IPR002885; Pentatricopeptide_repeat.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR037516; Tripartite_DENN.
DR InterPro; IPR005113; uDENN_dom.
DR Pfam; PF03455; dDENN; 1.
DR Pfam; PF02141; DENN; 1.
DR Pfam; PF03456; uDENN; 1.
DR SMART; SM00801; dDENN; 1.
DR SMART; SM00799; DENN; 1.
DR SMART; SM00800; uDENN; 1.
DR PROSITE; PS50211; DENN; 1.
DR PROSITE; PS51498; MABP; 1.
DR PROSITE; PS51375; PPR; 1.
PE 1: Evidence at protein level;
KW Golgi apparatus; Guanine-nucleotide releasing factor; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1496
FT /note="DENN domain-containing protein 4B"
FT /id="PRO_0000304678"
FT DOMAIN 44..203
FT /note="MABP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00831"
FT DOMAIN 195..369
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 390..526
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 528..644
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT REPEAT 775..811
FT /note="PPR 1"
FT REPEAT 812..846
FT /note="PPR 2"
FT REGION 720..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 891..970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 995..1055
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1067..1119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1205..1227
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 891..921
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1072..1090
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1105..1119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 953
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1092
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
SQ SEQUENCE 1496 AA; 163847 MW; A852570682E7C62A CRC64;
MAEERPPRLV DYFVVAGLAG NGAPIPEETW VPEPSGPLRP PRPAEPITDV AVIARALGEE
VPQGYTCIQA SAGGHPLELS AGLLGGTQPV ICYRRGRDKP PLVELGVLYE GKERPKPGFQ
VLDTTPYSHS ANLAPPGPGH PRTYLTYRRA AEGAGLHALG ITDLCLVLPS KGEGTPHTYC
RLPRNLNPGM WGPAVYLCYK VGLAKANTLV YEAELLGRYP EEDNEAFPLP ESVPVFCLPM
GATIECWPAQ TKYPVPVFST FVLTGAAGDK VYGAALQFYE AFPRARLSER QARALGLLSA
VERGRALGGR AVRSRRAIAV LSRWPAFPAF RAFLTFLYRY SVSGPHRLPL EAHISHFIHN
VPFPSPQRPR ILVQMSPYDN LLLCQPVSSP LPLSGASFLQ LLQSLGPELA ITLLLAVLTE
HKLLVHSLRP DLLTSVCEAL VSMIFPLHWQ CPYIPLCPLV LADVLSAPVP FIVGIHSSYF
DLHDPPADVI CVDLDTNTLF QTEEKKLLSP RTLPRRPYKV LLATLTNLYQ QLDQTYTGPE
EEASLEFLLT DYEAVCGRRA RLEREVQGAF LRFMACLLKG YRVFLRPLTQ APSEGARDVD
NLFFLQGFLK SRERSSHKLY SQLLHTQMFS QFIEECSFGS ARHAALEFFD SCVEKVHPEQ
EKPEPTPLVE LEELSGSELT VFITPPEEPA LPEGSESTPQ YCYDGFPELR AELFESLQEQ
PGALPVPGPS RSAPSSPAPR RTKQEMKVAQ RMAQKSAAVP ELWARCLLGH CYGLWFLCLP
AYVRSAPSRV QALHTAYHVL RQMESGKVVL PDEVCYRVLM QLCSHYGQPV LSVRVMLEMR
QAGIVPNTIT YGYYNKAVLE SKWPSGTPGG RLRWAKLRNV VLGAAQFRQP LRERQQQQQQ
QQQQQQQQQQ EQVSAHQEAG SSQAEPYLER PSPTRPLQRQ TTWAGRSLRD PASPPGRLVK
SGSLGSARGA QPTVEAGVAH MIEALGVLEP RGSPVPWHDG SLSDLSLTGE EPLPGGSPGG
SGSALSAQST EALEGLSGRG PKAGGRQDEA GTPRRGLGAR LQQLLTPSRH SPASRIPPPE
LPPDLPPPAR RSPMDSLLHP RERPGSTASE SSASLGSEWD LSESSLSNLS LRRSSERLSD
TPGSFQSPSL EILLSSCSLC RACDSLVYDE EIMAGWAPDD SNLNTTCPFC ACPFVPLLSV
QTLDSRPSVP SPKSAGASGS KDAPVPGGPG PVLSDRRLCL ALDEPQLCNG HMGGASRRVE
SGAWAYLSPL VLRKELESLV ENEGSEVLAL PELPSAHPII FWNLLWYFQR LRLPSILPGL
VLASCDGPSH SQAPSPWLTP DPASVQVRLL WDVLTPDPNS CPPLYVLWRV HSQIPQRVVW
PGPVPASLSL ALLESVLRHV GLNEVHKAVG LLLETLGPPP TGLHLQRGIY REILFLTMAA
LGKDHVDIVA FDKKYKSAFN KLASSMGKEE LRHRRAQMPT PKAIDCRKCF GAPPEC
