DEN2D_HUMAN
ID DEN2D_HUMAN Reviewed; 471 AA.
AC Q9H6A0; Q5T5V6; Q9BSU0;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=DENN domain-containing protein 2D;
GN Name=DENND2D;
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] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
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 MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [4]
RP FUNCTION AS GUANYL-NUCLEOTIDE EXCHANGE FACTOR.
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 [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23182661; DOI=10.1016/j.lungcan.2012.10.012;
RA Ling B., Zheng H., Fu G., Yuan J., Shi T., Chen S., Liu Y., Liu Y., Cao Y.,
RA Zheng S., Guo S., Han N., Gao Y., Cheng S., Zhang K.;
RT "Suppression of non-small cell lung cancer proliferation and tumorigenicity
RT by DENND2D.";
RL Lung Cancer 79:104-110(2013).
RN [6]
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 RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting
CC inactive GDP-bound Rab proteins into their active GTP-bound form.
CC {ECO:0000269|PubMed:20937701}.
CC -!- INTERACTION:
CC Q9H6A0; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-10307465, EBI-10175124;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23182661}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H6A0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H6A0-2; Sequence=VSP_019471;
CC -!- TISSUE SPECIFICITY: In bronchial mucosa, mainly expressed in ciliated
CC and basal epithelial cells and weakly in alveolar cells (at protein
CC level). Tends to be down-regulated in lung cancers, immortalized
CC bronchial epithelial cell lines and precancerous lesions.
CC {ECO:0000269|PubMed:23182661}.
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DR EMBL; AK026110; BAB15363.1; -; mRNA.
DR EMBL; AL355816; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004557; AAH04557.1; -; mRNA.
DR CCDS; CCDS60219.1; -. [Q9H6A0-2]
DR CCDS; CCDS831.1; -. [Q9H6A0-1]
DR RefSeq; NP_001258762.1; NM_001271833.1. [Q9H6A0-2]
DR RefSeq; NP_079177.2; NM_024901.4. [Q9H6A0-1]
DR AlphaFoldDB; Q9H6A0; -.
DR SMR; Q9H6A0; -.
DR BioGRID; 123030; 33.
DR IntAct; Q9H6A0; 24.
DR STRING; 9606.ENSP00000350266; -.
DR iPTMnet; Q9H6A0; -.
DR PhosphoSitePlus; Q9H6A0; -.
DR BioMuta; DENND2D; -.
DR DMDM; 109825794; -.
DR jPOST; Q9H6A0; -.
DR MassIVE; Q9H6A0; -.
DR MaxQB; Q9H6A0; -.
DR PaxDb; Q9H6A0; -.
DR PeptideAtlas; Q9H6A0; -.
DR PRIDE; Q9H6A0; -.
DR ProteomicsDB; 80967; -. [Q9H6A0-1]
DR ProteomicsDB; 80968; -. [Q9H6A0-2]
DR Antibodypedia; 53750; 78 antibodies from 12 providers.
DR DNASU; 79961; -.
DR Ensembl; ENST00000357640.9; ENSP00000350266.4; ENSG00000162777.17. [Q9H6A0-1]
DR Ensembl; ENST00000369752.5; ENSP00000358767.5; ENSG00000162777.17. [Q9H6A0-2]
DR GeneID; 79961; -.
DR KEGG; hsa:79961; -.
DR MANE-Select; ENST00000357640.9; ENSP00000350266.4; NM_024901.5; NP_079177.2.
DR UCSC; uc001eak.3; human. [Q9H6A0-1]
DR CTD; 79961; -.
DR DisGeNET; 79961; -.
DR GeneCards; DENND2D; -.
DR HGNC; HGNC:26192; DENND2D.
DR HPA; ENSG00000162777; Tissue enhanced (lymphoid).
DR MIM; 615111; gene.
DR neXtProt; NX_Q9H6A0; -.
DR OpenTargets; ENSG00000162777; -.
DR PharmGKB; PA142671986; -.
DR VEuPathDB; HostDB:ENSG00000162777; -.
DR eggNOG; KOG3569; Eukaryota.
DR GeneTree; ENSGT00950000182931; -.
DR HOGENOM; CLU_008196_5_1_1; -.
DR InParanoid; Q9H6A0; -.
DR OMA; CLFKNRV; -.
DR OrthoDB; 138384at2759; -.
DR PhylomeDB; Q9H6A0; -.
DR TreeFam; TF320336; -.
DR PathwayCommons; Q9H6A0; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q9H6A0; -.
DR BioGRID-ORCS; 79961; 18 hits in 1066 CRISPR screens.
DR ChiTaRS; DENND2D; human.
DR GenomeRNAi; 79961; -.
DR Pharos; Q9H6A0; Tbio.
DR PRO; PR:Q9H6A0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H6A0; protein.
DR Bgee; ENSG00000162777; Expressed in granulocyte and 149 other tissues.
DR ExpressionAtlas; Q9H6A0; baseline and differential.
DR Genevisible; Q9H6A0; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR Gene3D; 3.40.50.11500; -; 1.
DR InterPro; IPR001194; cDENN_dom.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR043153; DENN_C.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Guanine-nucleotide releasing factor;
KW Reference proteome.
FT CHAIN 1..471
FT /note="DENN domain-containing protein 2D"
FT /id="PRO_0000242686"
FT DOMAIN 55..204
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 226..359
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 361..445
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT VAR_SEQ 1..22
FT /note="MEGQVVGRVFRLFQRRLLQLRA -> MDGLGRRLRASLRLKRGHG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019471"
FT VARIANT 282
FT /note="S -> N (in dbSNP:rs35742969)"
FT /id="VAR_050950"
FT CONFLICT 185
FT /note="Y -> H (in Ref. 1; BAB15363)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 471 AA; 53672 MW; E885FA53369C738C CRC64;
MEGQVVGRVF RLFQRRLLQL RAGPPQDNSG EALKEPERAQ EHSLPNFAGG QHFFEYLLVV
SLKKKRSEDD YEPIITYQFP KRENLLRGQQ EEEERLLKAI PLFCFPDGNE WASLTEYPRE
TFSFVLTNVD GSRKIGYCRR LLPAGPGPRL PKVYCIISCI GCFGLFSKIL DEVEKRHQIS
MAVIYPFMQG LREAAFPAPG KTVTLKSFIP DSGTEFISLT RPLDSHLEHV DFSSLLHCLS
FEQILQIFAS AVLERKIIFL AEGLSTLSQC IHAAAALLYP FSWAHTYIPV VPESLLATVC
CPTPFMVGVQ MRFQQEVMDS PMEEVLLVNL CEGTFLMSVG DEKDILPPKL QDDILDSLGQ
GINELKTAEQ INEHVSGPFV QFFVKIVGHY ASYIKREANG QGHFQERSFC KALTSKTNRR
FVKKFVKTQL FSLFIQEAEK SKNPPAGYFQ QKILEYEEQK KQKKPREKTV K
