A2RUS2 (DEND3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DENN domain-containing protein 3

Gene names

Name:	DENND3
Synonyms:	KIAA0870

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1198 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form. Thereby, may play a role in protein transport from recycling endosomes to lysosomes regulating, for instance, the degradation of the transferrin receptor. Ref.5
Sequence similarities	Contains 1 dDENN domain. Contains 1 DENN domain. Contains 1 uDENN domain. Contains 3 WD repeats.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
Molecular function	Guanine-nucleotide releasing factor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB endosome to lysosome transport Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	Rab guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: A2RUS2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: A2RUS2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     319-370: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: A2RUS2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-950: Missing.
     1133-1198: VWVGSRGLGQ...EGKVAIWKGE → VGWRARHPQH...PNWMASNDRT

Note: No experimental confirmation available.

Isoform 4 (identifier: A2RUS2-4)

The sequence of this isoform differs from the canonical sequence as follows:
     128-128: C → W
     129-1198: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1198	1198	DENN domain-containing protein 3		PRO_0000304672
Regions
	Domain	6 – 83	78	UDENN
	Domain	105 – 291	187	DENN
	Domain	354 – 417	64	dDENN
	Repeat	984 – 1026	43	WD 1
	Repeat	1073 – 1113	41	WD 2
	Repeat	1165 – 1198	34	WD 3
Natural variations
	Alternative sequence	1 – 950	950	Missing in isoform 3.		VSP_028075
	Alternative sequence	128	1	C → W in isoform 4.		VSP_028077
	Alternative sequence	129 – 1198	1070	Missing in isoform 4.		VSP_028078
	Alternative sequence	319 – 370	52	Missing in isoform 2.		VSP_028080
	Alternative sequence	1133 – 1198	66	VWVGS…IWKGE → VGWRARHPQHPRQVSLALAA SPCSREPAARPRALLPSPLR VPLLTGTCRVGANGPTGHHV LVSWCGPSTPQRIPPNWMAS NDRT in isoform 3.		VSP_028081
	Natural variant	143	1	S → N. Corresponds to variant rs307761 [ dbSNP | Ensembl ].		VAR_035053
	Natural variant	364	1	Q → R. Corresponds to variant rs11997191 [ dbSNP | Ensembl ].		VAR_035054

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 11, 2007. Version 2. Checksum: 52D51635DDD88A4E	FASTA	1,198	135,890
	10 20 30 40 50 60 MRSLRKKREK PRPEQWKGLP GPPRAPEPED VAVPGGVDLL TLPQLCFPGG VCVATEPKED 70 80 90 100 110 120 CVHFLVLTDV CGNRTYGVVA QYYRPLHDEY CFYNGKTHRE CPGCFVPFAV CVVSRFPYYN 130 140 150 160 170 180 SLKDCLSCLL ALLKPCKDFE VDSHIKDFAA KLSLIPSPPP GPLHLVFNMK SLQIVLPARA 190 200 210 220 230 240 DPESPILDLD LHLPLLCFRP EKVLQILTCI LTEQRIVFFS SDWALLTLVT ECFMAYLYPL 250 260 270 280 290 300 QWQHPFVPIL SDQMLDFVMA PTSFLMGCHL DHFEEVSKEA DGLVLINIDH GSITYSKSTD 310 320 330 340 350 360 DNVDIPDVPL LAAQTFIQRV QSLQLHHELH AAHLLSSTDL KEGRAHRRSW QQKLNCQIQQ 370 380 390 400 410 420 TTLQLLVSIF RDVKNHLNYE HRVFNSEEFL KTRAPGDHQF YKQVLDTYMF HSFLKARLNR 430 440 450 460 470 480 RMDAFAQMDL DTQSEEDRIN GMLLSPRRPT VEKRASRKSS HLHVTHRRMV VSMPNLQDIA 490 500 510 520 530 540 MPELAPRNSS LRLTDTAGCR GSSAVLNVTP KSPYTFKIPE IHFPLESKCV QAYHAHFVSM 550 560 570 580 590 600 LSEAMCFLAP DNSLLLARYL YLRGLVYLMQ GQLLNALLDF QNLYKTDIRI FPTDLVKRTV 610 620 630 640 650 660 ESMSAPEWEG AEQAPELMRL ISEILDKPHE ASKLDDHVKK FKLPKKHMQL GDFMKRVQES 670 680 690 700 710 720 GIVKDASIIH RLFEALTVGQ EKQIDPETFK DFYNCWKETE AEAQEVSLPW LVMEHLDKNE 730 740 750 760 770 780 CVCKLSSSVK TNLGVGKIAM TQKRLFLLTE GRPGYLEIST FRNIEEVRRT TTTFLLRRIP 790 800 810 820 830 840 TLKIRVASKK EVFEANLKTE CDLWHLMVKE MWAGKKLADD HKDPHYVQQA LTNVLLMDAV 850 860 870 880 890 900 VGTLQSPGAI YAASKLSYFD KMSNEMPMTL PETTLETLKH KINPSAGEAF PQAVDVLLYT 910 920 930 940 950 960 PGHLDPAEKV EDAHPKLWCA LSEGKVTVFN ASSWTIHQHS FKVGTAKVNC MVMADQNQVW 970 980 990 1000 1010 1020 VGSEDSVIYI INVHSMSCNK QLTAHCSSVT DLIVQDGQEA PSNVYSCSMD GMVLVWNVST 1030 1040 1050 1060 1070 1080 LQVTSRFQLP RGGLTSIRLH GGRLWCCTGN SIMVMKMNGS LHQELKIEEN FKDTSTSFLA 1090 1100 1110 1120 1130 1140 FQLLPEEEQL WAACAGRSEV YIWSLKDLAQ PPQRVPLEDC SEINCMIRVK KQVWVGSRGL 1150 1160 1170 1180 1190 GQGTPKGKIY VIDAERKTVE KELVAHMDTV RTLCSAEDRY VLSGSGREEG KVAIWKGE
	Isoform 2 [UniParc]. Checksum: B8D7B60A600DDD0C	FASTA	1,146	129,809
	10 20 30 40 50 60 MRSLRKKREK PRPEQWKGLP GPPRAPEPED VAVPGGVDLL TLPQLCFPGG VCVATEPKED 70 80 90 100 110 120 CVHFLVLTDV CGNRTYGVVA QYYRPLHDEY CFYNGKTHRE CPGCFVPFAV CVVSRFPYYN 130 140 150 160 170 180 SLKDCLSCLL ALLKPCKDFE VDSHIKDFAA KLSLIPSPPP GPLHLVFNMK SLQIVLPARA 190 200 210 220 230 240 DPESPILDLD LHLPLLCFRP EKVLQILTCI LTEQRIVFFS SDWALLTLVT ECFMAYLYPL 250 260 270 280 290 300 QWQHPFVPIL SDQMLDFVMA PTSFLMGCHL DHFEEVSKEA DGLVLINIDH GSITYSKSTD 310 320 330 340 350 360 DNVDIPDVPL LAAQTFIQRD VKNHLNYEHR VFNSEEFLKT RAPGDHQFYK QVLDTYMFHS 370 380 390 400 410 420 FLKARLNRRM DAFAQMDLDT QSEEDRINGM LLSPRRPTVE KRASRKSSHL HVTHRRMVVS 430 440 450 460 470 480 MPNLQDIAMP ELAPRNSSLR LTDTAGCRGS SAVLNVTPKS PYTFKIPEIH FPLESKCVQA 490 500 510 520 530 540 YHAHFVSMLS EAMCFLAPDN SLLLARYLYL RGLVYLMQGQ LLNALLDFQN LYKTDIRIFP 550 560 570 580 590 600 TDLVKRTVES MSAPEWEGAE QAPELMRLIS EILDKPHEAS KLDDHVKKFK LPKKHMQLGD 610 620 630 640 650 660 FMKRVQESGI VKDASIIHRL FEALTVGQEK QIDPETFKDF YNCWKETEAE AQEVSLPWLV 670 680 690 700 710 720 MEHLDKNECV CKLSSSVKTN LGVGKIAMTQ KRLFLLTEGR PGYLEISTFR NIEEVRRTTT 730 740 750 760 770 780 TFLLRRIPTL KIRVASKKEV FEANLKTECD LWHLMVKEMW AGKKLADDHK DPHYVQQALT 790 800 810 820 830 840 NVLLMDAVVG TLQSPGAIYA ASKLSYFDKM SNEMPMTLPE TTLETLKHKI NPSAGEAFPQ 850 860 870 880 890 900 AVDVLLYTPG HLDPAEKVED AHPKLWCALS EGKVTVFNAS SWTIHQHSFK VGTAKVNCMV 910 920 930 940 950 960 MADQNQVWVG SEDSVIYIIN VHSMSCNKQL TAHCSSVTDL IVQDGQEAPS NVYSCSMDGM 970 980 990 1000 1010 1020 VLVWNVSTLQ VTSRFQLPRG GLTSIRLHGG RLWCCTGNSI MVMKMNGSLH QELKIEENFK 1030 1040 1050 1060 1070 1080 DTSTSFLAFQ LLPEEEQLWA ACAGRSEVYI WSLKDLAQPP QRVPLEDCSE INCMIRVKKQ 1090 1100 1110 1120 1130 1140 VWVGSRGLGQ GTPKGKIYVI DAERKTVEKE LVAHMDTVRT LCSAEDRYVL SGSGREEGKV AIWKGE
	Isoform 3 [UniParc]. Checksum: B5D62298848A4332	FASTA	266	29,486
	10 20 30 40 50 60 MVMADQNQVW VGSEDSVIYI INVHSMSCNK QLTAHCSSVT DLIVQDGQEA PSNVYSCSMD 70 80 90 100 110 120 GMVLVWNVST LQVTSRFQLP RGGLTSIRLH GGRLWCCTGN SIMVMKMNGS LHQELKIEEN 130 140 150 160 170 180 FKDTSTSFLA FQLLPEEEQL WAACAGRSEV YIWSLKDLAQ PPQRVPLEDC SEINCMIRVK 190 200 210 220 230 240 KQVGWRARHP QHPRQVSLAL AASPCSREPA ARPRALLPSP LRVPLLTGTC RVGANGPTGH 250 260 HVLVSWCGPS TPQRIPPNWM ASNDRT
	Isoform 4 [UniParc]. Checksum: B5E0DB642AC3F733	FASTA	128	14,509
	10 20 30 40 50 60 MRSLRKKREK PRPEQWKGLP GPPRAPEPED VAVPGGVDLL TLPQLCFPGG VCVATEPKED 70 80 90 100 110 120 CVHFLVLTDV CGNRTYGVVA QYYRPLHDEY CFYNGKTHRE CPGCFVPFAV CVVSRFPYYN SLKDCLSW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). Tissue: Gastric mucosa and Uterus.
[2]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 180-1146 (ISOFORM 1). Tissue: Brain.
[5]	"Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors." Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A. J. Cell Biol. 191:367-381(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS GUANYL-NUCLEOTIDE EXCHANGE FACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK058001 mRNA. Translation: BAB71630.1. AK131505 mRNA. Translation: BAD18649.1. AC040970 Genomic DNA. No translation available. BC133023 mRNA. Translation: AAI33024.1. BC144226 mRNA. Translation: AAI44227.1. AB020677 mRNA. Translation: BAA74893.2.
IPI	IPI00442078. IPI00448616. IPI00856077. IPI00981524.
RefSeq	NP_055772.2. NM_014957.2.
UniGene	Hs.18166.
3D structure databases
ProteinModelPortal	A2RUS2.
ModBase	Search...
Protein-protein interaction databases
IntAct	A2RUS2. 5 interactions.
STRING	9606.ENSP00000262585.
PTM databases
PhosphoSite	A2RUS2.
Proteomic databases
PaxDb	A2RUS2.
PRIDE	A2RUS2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262585; ENSP00000262585; ENSG00000105339. ENST00000424248; ENSP00000410594; ENSG00000105339.
GeneID	22898.
KEGG	hsa:22898.
UCSC	uc003yvy.3. human. uc003ywa.1. human. uc010mep.3. human.
Organism-specific databases
CTD	22898.
GeneCards	GC08P142156.
H-InvDB	HIX0007822.
HGNC	HGNC:29134. DENND3.
HPA	HPA026100.
neXtProt	NX_A2RUS2.
PharmGKB	PA142671987.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG115977.
HOGENOM	HOG000060114.
HOVERGEN	HBG095574.
InParanoid	A2RUS2.
OrthoDB	EOG4P8FH7.
Gene expression databases
ArrayExpress	A2RUS2.
Bgee	A2RUS2.
CleanEx	HS_DENND3.
Genevestigator	A2RUS2.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR005112. dDENN_dom. IPR001194. DENN_dom. IPR005113. uDENN_dom. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF03455. dDENN. 1 hit. PF02141. DENN. 1 hit. PF03456. uDENN. 1 hit. PF00400. WD40. 1 hit. [Graphical view]
SMART	SM00801. dDENN. 1 hit. SM00799. DENN. 1 hit. SM00320. WD40. 3 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS50947. DDENN. 1 hit. PS50211. DENN. 1 hit. PS50946. UDENN. 1 hit. PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. False negative. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	22898.
NextBio	43523.

Entry information

Entry name

DEND3_HUMAN

Accession

Primary (citable) accession number: A2RUS2
Secondary accession number(s): B7ZM28 , O94947, Q2TAM7, Q6ZMS6, Q96DK3

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	September 11, 2007
Last modified:	May 1, 2013
This is version 61 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.