Full text data of DENND1A
DENND1A
(FAM31A, KIAA1608)
[Confidence: low (only semi-automatic identification from reviews)]
DENN domain-containing protein 1A (Connecdenn 1; Connecdenn; Protein FAM31A)
DENN domain-containing protein 1A (Connecdenn 1; Connecdenn; Protein FAM31A)
UniProt
Q8TEH3
ID DEN1A_HUMAN Reviewed; 1009 AA.
AC Q8TEH3; A8MZA3; B1AM80; B7Z3C8; B7Z669; D3PFD3; Q05C88; Q5VWF0;
read moreAC Q6PJZ5; Q8IVD6; Q9H796;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 22-JAN-2014, entry version 82.
DE RecName: Full=DENN domain-containing protein 1A;
DE AltName: Full=Connecdenn 1;
DE Short=Connecdenn;
DE AltName: Full=Protein FAM31A;
GN Name=DENND1A; Synonyms=FAM31A, KIAA1608;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 6), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 114-1009 (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 217-1009 (ISOFORM 7).
RC TISSUE=Artery smooth muscle, Fetal brain, Hippocampus, and Spleen;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 5).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND MASS
RP SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-519; SER-520; SER-523;
RP SER-536; SER-538 AND SER-546, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538 AND SER-546, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP IDENTIFICATION (ISOFORM 1), FUNCTION, AND INTERACTION WITH AP2A2; CLTC
RP AND RAB35.
RX PubMed=20154091; DOI=10.1074/jbc.M109.050930;
RA Marat A.L., McPherson P.S.;
RT "The connecdenn family, Rab35 guanine nucleotide exchange factors
RT interfacing with the clathrin machinery.";
RL J. Biol. Chem. 285:10627-10637(2010).
RN [11]
RP FUNCTION, INTERACTION WITH CLATHRIN AND AP-2, AND SUBCELLULAR
RP 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-520; SER-523 AND
RP SER-592, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) regulating
CC clathrin-mediated endocytosis through RAB35 activation. Promotes
CC the exchange of GDP to GTP, converting inactive GDP-bound RAB35
CC into its active GTP-bound form. Regulates clathrin-mediated
CC endocytosis of synaptic vesicles.
CC -!- SUBUNIT: Interacts with ITSN1 AND SH3GL2 (By similarity).
CC Interacts with RAB35. Interacts with clathrin and with the adapter
CC protein complex 2, AP-2.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane; Peripheral membrane protein. Cell junction, synapse,
CC presynaptic cell membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q8TEH3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TEH3-2; Sequence=VSP_019464, VSP_019465;
CC Name=3;
CC IsoId=Q8TEH3-3; Sequence=VSP_034513, VSP_034514;
CC Name=4;
CC IsoId=Q8TEH3-4; Sequence=VSP_034509, VSP_034512, VSP_034513,
CC VSP_034514;
CC Name=5;
CC IsoId=Q8TEH3-5; Sequence=VSP_034510, VSP_034511, VSP_019464,
CC VSP_019465;
CC Name=6;
CC IsoId=Q8TEH3-6; Sequence=VSP_034509, VSP_040666, VSP_040668;
CC Note=No experimental confirmation available;
CC Name=7;
CC IsoId=Q8TEH3-7; Sequence=VSP_040667, VSP_040668;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Contains 1 dDENN domain.
CC -!- SIMILARITY: Contains 1 DENN domain.
CC -!- SIMILARITY: Contains 1 uDENN domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH09616.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAH28061.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAH13155.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AK024782; BAB15002.1; -; mRNA.
DR EMBL; AK074151; BAB84977.1; -; mRNA.
DR EMBL; AK295710; BAH12164.1; -; mRNA.
DR EMBL; AK299867; BAH13155.1; ALT_INIT; mRNA.
DR EMBL; AL445489; CAI39791.1; -; Genomic_DNA.
DR EMBL; AL161790; CAI39791.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI39791.1; JOINED; Genomic_DNA.
DR EMBL; AC006450; CAI39791.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI39792.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI39792.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI39792.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI39792.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAH73640.1; -; Genomic_DNA.
DR EMBL; AC006450; CAH73640.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAH73640.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAH73640.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI15705.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI15705.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI15705.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI15705.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI15706.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI15706.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI15706.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI15706.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI15707.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI15707.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI15707.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI15707.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAH73637.1; -; Genomic_DNA.
DR EMBL; AC006450; CAH73637.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAH73637.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAH73637.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAH73638.1; -; Genomic_DNA.
DR EMBL; AC006450; CAH73638.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAH73638.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAH73638.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI39794.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI39794.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI39794.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI39794.1; JOINED; Genomic_DNA.
DR EMBL; CH471090; EAW87571.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87575.1; -; Genomic_DNA.
DR EMBL; BC009616; AAH09616.1; ALT_INIT; mRNA.
DR EMBL; BC028061; AAH28061.1; ALT_INIT; mRNA.
DR EMBL; BC039703; AAH39703.1; -; mRNA.
DR EMBL; BK006958; DAA12500.1; -; mRNA.
DR RefSeq; NP_065997.1; NM_020946.1.
DR RefSeq; NP_079096.2; NM_024820.2.
DR RefSeq; XP_005252171.1; XM_005252114.1.
DR RefSeq; XP_005252172.1; XM_005252115.1.
DR UniGene; Hs.744995; -.
DR ProteinModelPortal; Q8TEH3; -.
DR SMR; Q8TEH3; 1-376.
DR IntAct; Q8TEH3; 1.
DR STRING; 9606.ENSP00000362727; -.
DR PhosphoSite; Q8TEH3; -.
DR DMDM; 109825594; -.
DR PaxDb; Q8TEH3; -.
DR PRIDE; Q8TEH3; -.
DR DNASU; 57706; -.
DR Ensembl; ENST00000373618; ENSP00000362720; ENSG00000119522.
DR Ensembl; ENST00000373620; ENSP00000362722; ENSG00000119522.
DR Ensembl; ENST00000373624; ENSP00000362727; ENSG00000119522.
DR Ensembl; ENST00000394215; ENSP00000377763; ENSG00000119522.
DR Ensembl; ENST00000394219; ENSP00000377766; ENSG00000119522.
DR Ensembl; ENST00000542603; ENSP00000437457; ENSG00000119522.
DR GeneID; 57706; -.
DR KEGG; hsa:57706; -.
DR UCSC; uc004bnz.1; human.
DR CTD; 57706; -.
DR GeneCards; GC09M126141; -.
DR H-InvDB; HIX0008366; -.
DR HGNC; HGNC:29324; DENND1A.
DR HPA; HPA020481; -.
DR MIM; 613633; gene.
DR neXtProt; NX_Q8TEH3; -.
DR PharmGKB; PA134876117; -.
DR eggNOG; NOG316099; -.
DR HOVERGEN; HBG059210; -.
DR OMA; SISSPEX; -.
DR OrthoDB; EOG73Z2SH; -.
DR ChiTaRS; DENND1A; human.
DR GeneWiki; DENND1A; -.
DR GenomeRNAi; 57706; -.
DR NextBio; 64584; -.
DR PRO; PR:Q8TEH3; -.
DR Bgee; Q8TEH3; -.
DR CleanEx; HS_DENND1A; -.
DR Genevestigator; Q8TEH3; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017112; F:Rab guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IEA:Ensembl.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR001194; DENN_dom.
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; PS50947; DDENN; 1.
DR PROSITE; PS50211; DENN; 1.
DR PROSITE; PS50946; UDENN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Complete proteome;
KW Cytoplasmic vesicle; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Synapse;
KW Transport.
FT CHAIN 1 1009 DENN domain-containing protein 1A.
FT /FTId=PRO_0000242680.
FT DOMAIN 24 91 UDENN.
FT DOMAIN 92 273 DENN.
FT DOMAIN 304 371 dDENN.
FT COMPBIAS 649 995 Pro-rich.
FT MOD_RES 473 473 Phosphoserine (By similarity).
FT MOD_RES 519 519 Phosphothreonine.
FT MOD_RES 520 520 Phosphoserine.
FT MOD_RES 523 523 Phosphoserine.
FT MOD_RES 536 536 Phosphoserine.
FT MOD_RES 538 538 Phosphoserine.
FT MOD_RES 546 546 Phosphoserine.
FT MOD_RES 592 592 Phosphoserine.
FT VAR_SEQ 1 32 Missing (in isoform 4 and isoform 6).
FT /FTId=VSP_034509.
FT VAR_SEQ 1 30 Missing (in isoform 5).
FT /FTId=VSP_034510.
FT VAR_SEQ 31 43 PEVQRQFPEDYSD -> MLKWPIPGQVALF (in
FT isoform 5).
FT /FTId=VSP_034511.
FT VAR_SEQ 33 60 VQRQFPEDYSDQEVLQTLTKFCFPFYVD -> MLKWPIPGQ
FT VALFQILRCRGNSRRTTVT (in isoform 4).
FT /FTId=VSP_034512.
FT VAR_SEQ 33 42 VQRQFPEDYS -> MRRPGDHGLQ (in isoform 6).
FT /FTId=VSP_040666.
FT VAR_SEQ 290 331 Missing (in isoform 7).
FT /FTId=VSP_040667.
FT VAR_SEQ 497 498 VR -> AL (in isoform 3 and isoform 4).
FT /FTId=VSP_034513.
FT VAR_SEQ 499 1009 Missing (in isoform 3 and isoform 4).
FT /FTId=VSP_034514.
FT VAR_SEQ 526 526 Q -> HLVKPLRHYAVFLSEDSSDDECQREEGPSSGFTESF
FT FFSAPFEW (in isoform 6 and isoform 7).
FT /FTId=VSP_040668.
FT VAR_SEQ 527 559 PQPYRTLRESDSAEGDEAESPEQQVRKSTGPVP -> NTIA
FT TPATLHILQKSITHFAAKFPTRGWTSSSH (in isoform
FT 2 and isoform 5).
FT /FTId=VSP_019464.
FT VAR_SEQ 560 1009 Missing (in isoform 2 and isoform 5).
FT /FTId=VSP_019465.
FT CONFLICT 456 456 E -> G (in Ref. 1; BAB15002).
SQ SEQUENCE 1009 AA; 110577 MW; ECEE79CFCD5E2D0C CRC64;
MGSRIKQNPE TTFEVYVEVA YPRTGGTLSD PEVQRQFPED YSDQEVLQTL TKFCFPFYVD
SLTVSQVGQN FTFVLTDIDS KQRFGFCRLS SGAKSCFCIL SYLPWFEVFY KLLNILADYT
TKRQENQWNE LLETLHKLPI PDPGVSVHLS VHSYFTVPDT RELPSIPENR NLTEYFVAVD
VNNMLHLYAS MLYERRILII CSKLSTLTAC IHGSAAMLYP MYWQHVYIPV LPPHLLDYCC
APMPYLIGIH LSLMEKVRNM ALDDVVILNV DTNTLETPFD DLQSLPNDVI SSLKNRLKKV
STTTGDGVAR AFLKAQAAFF GSYRNALKIE PEEPITFCEE AFVSHYRSGA MRQFLQNATQ
LQLFKQFIDG RLDLLNSGEG FSDVFEEEIN MGEYAGSDKL YHQWLSTVRK GSGAILNTVK
TKANPAMKTV YKFAKDHAKM GIKEVKNRLK QKDIAENGCA PTPEEQLPKT APSPLVEAKD
PKLREDRRPI TVHFGQVRPP RPHVVKRPKS NIAVEGRRTS VPSPEQPQPY RTLRESDSAE
GDEAESPEQQ VRKSTGPVPA PPDRAASIDL LEDVFSNLDM EAALQPLGQA KSLEDLRAPK
DLREQPGTFD YQRLDLGGSE RSRGVTVALK LTHPYNKLWS LGQDDMAIPS KPPAASPEKP
SALLGNSLAL PRRPQNRDSI LNPSDKEEVP TPTLGSITIP RPQGRKTPEL GIVPPPPIPR
PAKLQAAGAA LGDVSERLQT DRDRRAALSP GLLPGVVPQG PTELLQPLSP GPGAAGTSSD
ALLALLDPLS TAWSGSTLPS RPATPNVATP FTPQFSFPPA GTPTPFPQPP LNPFVPSMPA
APPTLPLVST PAGPFGAPPA SLGPAFASGL LLSSAGFCAP HRSQPNLSAL SMPNLFGQMP
MGTHTSPLQP LGPPAVAPSR IRTLPLARSS ARAAETKQGL ALRPGDPPLL PPRPPQGLEP
TLQPSAPQQA RDPFEDLLQK TKQDVSPSPA LAPAPDSVEQ LRKQWETFE
//
ID DEN1A_HUMAN Reviewed; 1009 AA.
AC Q8TEH3; A8MZA3; B1AM80; B7Z3C8; B7Z669; D3PFD3; Q05C88; Q5VWF0;
read moreAC Q6PJZ5; Q8IVD6; Q9H796;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 22-JAN-2014, entry version 82.
DE RecName: Full=DENN domain-containing protein 1A;
DE AltName: Full=Connecdenn 1;
DE Short=Connecdenn;
DE AltName: Full=Protein FAM31A;
GN Name=DENND1A; Synonyms=FAM31A, KIAA1608;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 6), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 114-1009 (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 217-1009 (ISOFORM 7).
RC TISSUE=Artery smooth muscle, Fetal brain, Hippocampus, and Spleen;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 5).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND MASS
RP SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-519; SER-520; SER-523;
RP SER-536; SER-538 AND SER-546, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538 AND SER-546, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP IDENTIFICATION (ISOFORM 1), FUNCTION, AND INTERACTION WITH AP2A2; CLTC
RP AND RAB35.
RX PubMed=20154091; DOI=10.1074/jbc.M109.050930;
RA Marat A.L., McPherson P.S.;
RT "The connecdenn family, Rab35 guanine nucleotide exchange factors
RT interfacing with the clathrin machinery.";
RL J. Biol. Chem. 285:10627-10637(2010).
RN [11]
RP FUNCTION, INTERACTION WITH CLATHRIN AND AP-2, AND SUBCELLULAR
RP 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-520; SER-523 AND
RP SER-592, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) regulating
CC clathrin-mediated endocytosis through RAB35 activation. Promotes
CC the exchange of GDP to GTP, converting inactive GDP-bound RAB35
CC into its active GTP-bound form. Regulates clathrin-mediated
CC endocytosis of synaptic vesicles.
CC -!- SUBUNIT: Interacts with ITSN1 AND SH3GL2 (By similarity).
CC Interacts with RAB35. Interacts with clathrin and with the adapter
CC protein complex 2, AP-2.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane; Peripheral membrane protein. Cell junction, synapse,
CC presynaptic cell membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q8TEH3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TEH3-2; Sequence=VSP_019464, VSP_019465;
CC Name=3;
CC IsoId=Q8TEH3-3; Sequence=VSP_034513, VSP_034514;
CC Name=4;
CC IsoId=Q8TEH3-4; Sequence=VSP_034509, VSP_034512, VSP_034513,
CC VSP_034514;
CC Name=5;
CC IsoId=Q8TEH3-5; Sequence=VSP_034510, VSP_034511, VSP_019464,
CC VSP_019465;
CC Name=6;
CC IsoId=Q8TEH3-6; Sequence=VSP_034509, VSP_040666, VSP_040668;
CC Note=No experimental confirmation available;
CC Name=7;
CC IsoId=Q8TEH3-7; Sequence=VSP_040667, VSP_040668;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Contains 1 dDENN domain.
CC -!- SIMILARITY: Contains 1 DENN domain.
CC -!- SIMILARITY: Contains 1 uDENN domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH09616.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAH28061.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAH13155.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AK024782; BAB15002.1; -; mRNA.
DR EMBL; AK074151; BAB84977.1; -; mRNA.
DR EMBL; AK295710; BAH12164.1; -; mRNA.
DR EMBL; AK299867; BAH13155.1; ALT_INIT; mRNA.
DR EMBL; AL445489; CAI39791.1; -; Genomic_DNA.
DR EMBL; AL161790; CAI39791.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI39791.1; JOINED; Genomic_DNA.
DR EMBL; AC006450; CAI39791.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI39792.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI39792.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI39792.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI39792.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAH73640.1; -; Genomic_DNA.
DR EMBL; AC006450; CAH73640.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAH73640.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAH73640.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI15705.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI15705.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI15705.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI15705.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI15706.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI15706.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI15706.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI15706.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI15707.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI15707.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI15707.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI15707.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAH73637.1; -; Genomic_DNA.
DR EMBL; AC006450; CAH73637.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAH73637.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAH73637.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAH73638.1; -; Genomic_DNA.
DR EMBL; AC006450; CAH73638.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAH73638.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAH73638.1; JOINED; Genomic_DNA.
DR EMBL; AL445489; CAI39794.1; -; Genomic_DNA.
DR EMBL; AC006450; CAI39794.1; JOINED; Genomic_DNA.
DR EMBL; AL161790; CAI39794.1; JOINED; Genomic_DNA.
DR EMBL; AL390774; CAI39794.1; JOINED; Genomic_DNA.
DR EMBL; CH471090; EAW87571.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87575.1; -; Genomic_DNA.
DR EMBL; BC009616; AAH09616.1; ALT_INIT; mRNA.
DR EMBL; BC028061; AAH28061.1; ALT_INIT; mRNA.
DR EMBL; BC039703; AAH39703.1; -; mRNA.
DR EMBL; BK006958; DAA12500.1; -; mRNA.
DR RefSeq; NP_065997.1; NM_020946.1.
DR RefSeq; NP_079096.2; NM_024820.2.
DR RefSeq; XP_005252171.1; XM_005252114.1.
DR RefSeq; XP_005252172.1; XM_005252115.1.
DR UniGene; Hs.744995; -.
DR ProteinModelPortal; Q8TEH3; -.
DR SMR; Q8TEH3; 1-376.
DR IntAct; Q8TEH3; 1.
DR STRING; 9606.ENSP00000362727; -.
DR PhosphoSite; Q8TEH3; -.
DR DMDM; 109825594; -.
DR PaxDb; Q8TEH3; -.
DR PRIDE; Q8TEH3; -.
DR DNASU; 57706; -.
DR Ensembl; ENST00000373618; ENSP00000362720; ENSG00000119522.
DR Ensembl; ENST00000373620; ENSP00000362722; ENSG00000119522.
DR Ensembl; ENST00000373624; ENSP00000362727; ENSG00000119522.
DR Ensembl; ENST00000394215; ENSP00000377763; ENSG00000119522.
DR Ensembl; ENST00000394219; ENSP00000377766; ENSG00000119522.
DR Ensembl; ENST00000542603; ENSP00000437457; ENSG00000119522.
DR GeneID; 57706; -.
DR KEGG; hsa:57706; -.
DR UCSC; uc004bnz.1; human.
DR CTD; 57706; -.
DR GeneCards; GC09M126141; -.
DR H-InvDB; HIX0008366; -.
DR HGNC; HGNC:29324; DENND1A.
DR HPA; HPA020481; -.
DR MIM; 613633; gene.
DR neXtProt; NX_Q8TEH3; -.
DR PharmGKB; PA134876117; -.
DR eggNOG; NOG316099; -.
DR HOVERGEN; HBG059210; -.
DR OMA; SISSPEX; -.
DR OrthoDB; EOG73Z2SH; -.
DR ChiTaRS; DENND1A; human.
DR GeneWiki; DENND1A; -.
DR GenomeRNAi; 57706; -.
DR NextBio; 64584; -.
DR PRO; PR:Q8TEH3; -.
DR Bgee; Q8TEH3; -.
DR CleanEx; HS_DENND1A; -.
DR Genevestigator; Q8TEH3; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017112; F:Rab guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IEA:Ensembl.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR001194; DENN_dom.
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; PS50947; DDENN; 1.
DR PROSITE; PS50211; DENN; 1.
DR PROSITE; PS50946; UDENN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Complete proteome;
KW Cytoplasmic vesicle; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Synapse;
KW Transport.
FT CHAIN 1 1009 DENN domain-containing protein 1A.
FT /FTId=PRO_0000242680.
FT DOMAIN 24 91 UDENN.
FT DOMAIN 92 273 DENN.
FT DOMAIN 304 371 dDENN.
FT COMPBIAS 649 995 Pro-rich.
FT MOD_RES 473 473 Phosphoserine (By similarity).
FT MOD_RES 519 519 Phosphothreonine.
FT MOD_RES 520 520 Phosphoserine.
FT MOD_RES 523 523 Phosphoserine.
FT MOD_RES 536 536 Phosphoserine.
FT MOD_RES 538 538 Phosphoserine.
FT MOD_RES 546 546 Phosphoserine.
FT MOD_RES 592 592 Phosphoserine.
FT VAR_SEQ 1 32 Missing (in isoform 4 and isoform 6).
FT /FTId=VSP_034509.
FT VAR_SEQ 1 30 Missing (in isoform 5).
FT /FTId=VSP_034510.
FT VAR_SEQ 31 43 PEVQRQFPEDYSD -> MLKWPIPGQVALF (in
FT isoform 5).
FT /FTId=VSP_034511.
FT VAR_SEQ 33 60 VQRQFPEDYSDQEVLQTLTKFCFPFYVD -> MLKWPIPGQ
FT VALFQILRCRGNSRRTTVT (in isoform 4).
FT /FTId=VSP_034512.
FT VAR_SEQ 33 42 VQRQFPEDYS -> MRRPGDHGLQ (in isoform 6).
FT /FTId=VSP_040666.
FT VAR_SEQ 290 331 Missing (in isoform 7).
FT /FTId=VSP_040667.
FT VAR_SEQ 497 498 VR -> AL (in isoform 3 and isoform 4).
FT /FTId=VSP_034513.
FT VAR_SEQ 499 1009 Missing (in isoform 3 and isoform 4).
FT /FTId=VSP_034514.
FT VAR_SEQ 526 526 Q -> HLVKPLRHYAVFLSEDSSDDECQREEGPSSGFTESF
FT FFSAPFEW (in isoform 6 and isoform 7).
FT /FTId=VSP_040668.
FT VAR_SEQ 527 559 PQPYRTLRESDSAEGDEAESPEQQVRKSTGPVP -> NTIA
FT TPATLHILQKSITHFAAKFPTRGWTSSSH (in isoform
FT 2 and isoform 5).
FT /FTId=VSP_019464.
FT VAR_SEQ 560 1009 Missing (in isoform 2 and isoform 5).
FT /FTId=VSP_019465.
FT CONFLICT 456 456 E -> G (in Ref. 1; BAB15002).
SQ SEQUENCE 1009 AA; 110577 MW; ECEE79CFCD5E2D0C CRC64;
MGSRIKQNPE TTFEVYVEVA YPRTGGTLSD PEVQRQFPED YSDQEVLQTL TKFCFPFYVD
SLTVSQVGQN FTFVLTDIDS KQRFGFCRLS SGAKSCFCIL SYLPWFEVFY KLLNILADYT
TKRQENQWNE LLETLHKLPI PDPGVSVHLS VHSYFTVPDT RELPSIPENR NLTEYFVAVD
VNNMLHLYAS MLYERRILII CSKLSTLTAC IHGSAAMLYP MYWQHVYIPV LPPHLLDYCC
APMPYLIGIH LSLMEKVRNM ALDDVVILNV DTNTLETPFD DLQSLPNDVI SSLKNRLKKV
STTTGDGVAR AFLKAQAAFF GSYRNALKIE PEEPITFCEE AFVSHYRSGA MRQFLQNATQ
LQLFKQFIDG RLDLLNSGEG FSDVFEEEIN MGEYAGSDKL YHQWLSTVRK GSGAILNTVK
TKANPAMKTV YKFAKDHAKM GIKEVKNRLK QKDIAENGCA PTPEEQLPKT APSPLVEAKD
PKLREDRRPI TVHFGQVRPP RPHVVKRPKS NIAVEGRRTS VPSPEQPQPY RTLRESDSAE
GDEAESPEQQ VRKSTGPVPA PPDRAASIDL LEDVFSNLDM EAALQPLGQA KSLEDLRAPK
DLREQPGTFD YQRLDLGGSE RSRGVTVALK LTHPYNKLWS LGQDDMAIPS KPPAASPEKP
SALLGNSLAL PRRPQNRDSI LNPSDKEEVP TPTLGSITIP RPQGRKTPEL GIVPPPPIPR
PAKLQAAGAA LGDVSERLQT DRDRRAALSP GLLPGVVPQG PTELLQPLSP GPGAAGTSSD
ALLALLDPLS TAWSGSTLPS RPATPNVATP FTPQFSFPPA GTPTPFPQPP LNPFVPSMPA
APPTLPLVST PAGPFGAPPA SLGPAFASGL LLSSAGFCAP HRSQPNLSAL SMPNLFGQMP
MGTHTSPLQP LGPPAVAPSR IRTLPLARSS ARAAETKQGL ALRPGDPPLL PPRPPQGLEP
TLQPSAPQQA RDPFEDLLQK TKQDVSPSPA LAPAPDSVEQ LRKQWETFE
//
MIM
613633
*RECORD*
*FIELD* NO
613633
*FIELD* TI
*613633 DENN/MADD DOMAIN-CONTAINING PROTEIN 1A; DENND1A
;;CONNECDENN;;
CONNECDENN 1;;
read moreKIAA1608
*FIELD* TX
DESCRIPTION
Clathrin (see 118955)-mediated endocytosis is a major mechanism for
internalization of proteins and lipids. Members of the connecdenn
family, such as DENND1A, function as guanine nucleotide exchange factors
(GEFs) for the early endosomal small GTPase RAB35 (604199) and bind to
clathrin and clathrin adaptor protein-2 (AP2; see 601024). Thus,
connecdenns link RAB35 activation with the clathrin machinery (Marat and
McPherson, 2010).
CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA
library, Nagase et al. (2000) obtained a partial DENND1A clone, which
they designated KIAA1608. RT-PCR ELISA detected ubiquitous DENND1A
expression, with highest levels in adult and fetal brain and adult
kidney. Within specific adult brain regions, highest expression was
detected in hippocampus and thalamus.
By database analysis, Allaire et al. (2006) identified mouse Dennd1a,
which they called connecdenn. The deduced 1,016-amino acid protein
contains an N-terminal DENN domain composed of 3 DENN modules, followed
by a PxxP-rich domain. Connecdenn also contains 3 motifs, FSDVF, DPF,
and WETFE, for binding to the alpha ear of AP2. Western blot analysis of
rat tissues detected connecdenn in brain and testis, but not in several
other tissues, including kidney. Immunofluorescence microscopy of
cultured rat brain hippocampal neurons showed connecdenn in neuronal
cell bodies and along dendrites in a punctate distribution, where it
partly colocalized with the presynaptic marker synaptophysin (SYP;
313475).
Marat and McPherson (2010) reported that the human connecdenn-1 protein
contains 1,009 amino acids. It shares 38% and 32% amino acid identity
with human connecdenn-2 (DENND1B; 613292) and -3 (DENND1C; 613634),
respectively.
GENE FUNCTION
Using coimmunoprecipitation analysis and protein-binding assays, Allaire
et al. (2006) found that connecdenn bound rat brain AP2. Mutation
analysis revealed that the WETFE motif of connecdenn predominantly
mediated binding to the alpha-ear motif of AP2, but that the DPF and
FSDVF motifs also contributed. The isolated PxxP domain of connecdenn
bound the SH3 domains of endophilin A1 (SH3GL2; 604465) and the
endocytic adaptor protein intersectin (ITSN1; 602442), but it did not
bind to other SH3 domain-containing proteins. Connecdenn also
coimmunoprecipitated with rat brain intersectin and endophilin A1 and
was enriched with clathrin-coated vesicles to the same extent as
clathrin heavy chain (CLTC; 118955) and AP2. Overexpression and
knockdown studies revealed that connecdenn has a role in synaptic
vesicle endocytosis.
Using a protein pull-down assay with rat brain lysates, Marat and
McPherson (2010) showed that connecdenn-1, -2, and -3 bound the terminal
domain of clathrin heavy chain. The isolated DENN domains of
connecdenn-1 and -2 bound the GDP-bound form of RAB35, and the DENN
domains of all 3 connecdenns functioned as GEFs for RAB35. All 3
connecdenns copurified with rat brain clathrin-coated vesicles, although
connecdenn-2 and -3 also showed a substantial cytosolic pool. Knockdown
of connecdenn-1 or -2 or Rab35 in COS-7 cells resulted in perinuclear
clustering and enlargement of early endosomes.
MAPPING
By radiation hybrid analysis, Nagase et al. (2000) mapped the DENND1A
gene to chromosome 9. Marat and McPherson (2010) stated that the DENND1A
gene maps to chromosome 9q33.2.
*FIELD* RF
1. Allaire, P. D.; Ritter, B.; Thomas, S.; Burman, J. L.; Denisov,
A. Y.; Legendre-Guillemin, V.; Harper, S. Q.; Davidson, B. L.; Gehring,
K.; McPherson, P. S.: Connecdenn, a novel DENN domain-containing
protein of neuronal clathrin-coated vesicles functioning in synaptic
vesicle endocytosis. J. Neurosci. 26: 13202-13212, 2006.
2. Marat, A. L.; McPherson, P. S.: The connecdenn family, Rab35 guanine
nucleotide exchange factors interfacing with the clathrin machinery. J.
Biol. Chem. 285: 10627-10637, 2010.
3. Nagase, T.; Kikuno, R.; Nakayama, M.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVIII.
The complete sequences of 100 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 273-281, 2000.
*FIELD* CD
Patricia A. Hartz: 11/9/2010
*FIELD* ED
mgross: 11/09/2010
*RECORD*
*FIELD* NO
613633
*FIELD* TI
*613633 DENN/MADD DOMAIN-CONTAINING PROTEIN 1A; DENND1A
;;CONNECDENN;;
CONNECDENN 1;;
read moreKIAA1608
*FIELD* TX
DESCRIPTION
Clathrin (see 118955)-mediated endocytosis is a major mechanism for
internalization of proteins and lipids. Members of the connecdenn
family, such as DENND1A, function as guanine nucleotide exchange factors
(GEFs) for the early endosomal small GTPase RAB35 (604199) and bind to
clathrin and clathrin adaptor protein-2 (AP2; see 601024). Thus,
connecdenns link RAB35 activation with the clathrin machinery (Marat and
McPherson, 2010).
CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA
library, Nagase et al. (2000) obtained a partial DENND1A clone, which
they designated KIAA1608. RT-PCR ELISA detected ubiquitous DENND1A
expression, with highest levels in adult and fetal brain and adult
kidney. Within specific adult brain regions, highest expression was
detected in hippocampus and thalamus.
By database analysis, Allaire et al. (2006) identified mouse Dennd1a,
which they called connecdenn. The deduced 1,016-amino acid protein
contains an N-terminal DENN domain composed of 3 DENN modules, followed
by a PxxP-rich domain. Connecdenn also contains 3 motifs, FSDVF, DPF,
and WETFE, for binding to the alpha ear of AP2. Western blot analysis of
rat tissues detected connecdenn in brain and testis, but not in several
other tissues, including kidney. Immunofluorescence microscopy of
cultured rat brain hippocampal neurons showed connecdenn in neuronal
cell bodies and along dendrites in a punctate distribution, where it
partly colocalized with the presynaptic marker synaptophysin (SYP;
313475).
Marat and McPherson (2010) reported that the human connecdenn-1 protein
contains 1,009 amino acids. It shares 38% and 32% amino acid identity
with human connecdenn-2 (DENND1B; 613292) and -3 (DENND1C; 613634),
respectively.
GENE FUNCTION
Using coimmunoprecipitation analysis and protein-binding assays, Allaire
et al. (2006) found that connecdenn bound rat brain AP2. Mutation
analysis revealed that the WETFE motif of connecdenn predominantly
mediated binding to the alpha-ear motif of AP2, but that the DPF and
FSDVF motifs also contributed. The isolated PxxP domain of connecdenn
bound the SH3 domains of endophilin A1 (SH3GL2; 604465) and the
endocytic adaptor protein intersectin (ITSN1; 602442), but it did not
bind to other SH3 domain-containing proteins. Connecdenn also
coimmunoprecipitated with rat brain intersectin and endophilin A1 and
was enriched with clathrin-coated vesicles to the same extent as
clathrin heavy chain (CLTC; 118955) and AP2. Overexpression and
knockdown studies revealed that connecdenn has a role in synaptic
vesicle endocytosis.
Using a protein pull-down assay with rat brain lysates, Marat and
McPherson (2010) showed that connecdenn-1, -2, and -3 bound the terminal
domain of clathrin heavy chain. The isolated DENN domains of
connecdenn-1 and -2 bound the GDP-bound form of RAB35, and the DENN
domains of all 3 connecdenns functioned as GEFs for RAB35. All 3
connecdenns copurified with rat brain clathrin-coated vesicles, although
connecdenn-2 and -3 also showed a substantial cytosolic pool. Knockdown
of connecdenn-1 or -2 or Rab35 in COS-7 cells resulted in perinuclear
clustering and enlargement of early endosomes.
MAPPING
By radiation hybrid analysis, Nagase et al. (2000) mapped the DENND1A
gene to chromosome 9. Marat and McPherson (2010) stated that the DENND1A
gene maps to chromosome 9q33.2.
*FIELD* RF
1. Allaire, P. D.; Ritter, B.; Thomas, S.; Burman, J. L.; Denisov,
A. Y.; Legendre-Guillemin, V.; Harper, S. Q.; Davidson, B. L.; Gehring,
K.; McPherson, P. S.: Connecdenn, a novel DENN domain-containing
protein of neuronal clathrin-coated vesicles functioning in synaptic
vesicle endocytosis. J. Neurosci. 26: 13202-13212, 2006.
2. Marat, A. L.; McPherson, P. S.: The connecdenn family, Rab35 guanine
nucleotide exchange factors interfacing with the clathrin machinery. J.
Biol. Chem. 285: 10627-10637, 2010.
3. Nagase, T.; Kikuno, R.; Nakayama, M.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVIII.
The complete sequences of 100 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 273-281, 2000.
*FIELD* CD
Patricia A. Hartz: 11/9/2010
*FIELD* ED
mgross: 11/09/2010