Q86UW9 (DTX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable E3 ubiquitin-protein ligase DTX2
EC=6.3.2.-

Alternative name(s):
Protein deltex-2
Short name=Deltex2
Short name=hDTX2
RING finger protein 58

Gene names

Name:	DTX2
Synonyms:	KIAA1528, RNF58

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	622 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as an ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1 By similarity. Ref.1
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Partially nuclear. Ref.6
Domain	The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases By similarity.
Sequence similarities	Belongs to the Deltex family. Contains 1 RING-type zinc finger. Contains 2 WWE domains.
Sequence caution	The sequence BAA96052.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Notch signaling pathway Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear membrane Inferred from direct assay. Source: HPA
Molecular_function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2D4	Q9Y2X8	3	EBI-740376,EBI-745527

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86UW9-1)

Also known as: A;

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: Q86UW9-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     337-383: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 622	622	Probable E3 ubiquitin-protein ligase DTX2		PRO_0000219083
Regions
	Domain	8 – 97	90	WWE 1
	Domain	98 – 174	77	WWE 2
	Zinc finger	412 – 473	62	RING-type
Natural variations
	Alternative sequence	337 – 383	47	Missing in isoform 2.		VSP_008350
	Natural variant	94	1	A → T. Corresponds to variant rs2462312 [ dbSNP | Ensembl ].		VAR_016920
	Natural variant	384	1	G → E. Ref.1 Ref.2 Ref.5 Corresponds to variant rs1638152 [ dbSNP | Ensembl ].		VAR_016921
	Natural variant	421	1	T → A. Ref.2 Ref.3 Corresponds to variant rs6979487 [ dbSNP | Ensembl ].		VAR_016922

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified June 21, 2005. Version 3. Checksum: ABE1398204F2273A	FASTA	622	67,246
	10 20 30 40 50 60 MAMAPSPSLV QVYTSPAAVA VWEWQDGLGT WHPYSATVCS FIEQQFVQQK GQRFGLGSLA 70 80 90 100 110 120 HSIPLGQADP SLAPYIIDLP SWTQFRQDTG TMRAVRRHLF PQHSAPGRGV VWEWLSDDGS 130 140 150 160 170 180 WTAYEASVCD YLEQQVARGN QLVDLAPLGY NYTVNYTTHT QTNKTSSFCR SVRRQAGPPY 190 200 210 220 230 240 PVTTIIAPPG HTGVACSCHQ CLSGSRTGPV SGRYRHSMTN LPAYPVPQHP PHRTASVFGT 250 260 270 280 290 300 HQAFAPYNKP SLSGARSAPR LNTTNAWGAA PPSLGSQPLY RSSLSHLGPQ HLPPGSSTSG 310 320 330 340 350 360 AVSASLPSGP SSSPGSVPAT VPMQMPKPSR VQQALAGMTS VLMSAIGLPV CLSRAPQPTS 370 380 390 400 410 420 PPASRLASKS HGSVKRLRKM SVKGATPKPE PEPEQVIKNY TEELKVPPDE DCIICMEKLS 430 440 450 460 470 480 TASGYSDVTD SKAIGSLAVG HLTKCSHAFH LLCLLAMYCN GNKDGSLQCP SCKTIYGEKT 490 500 510 520 530 540 GTQPQGKMEV LRFQMSLPGH EDCGTILIVY SIPHGIQGPE HPNPGKPFTA RGFPRQCYLP 550 560 570 580 590 600 DNAQGRKVLE LLKVAWKRRL IFTVGTSSTT GETDTVVWNE IHHKTEMDRN ITGHGYPDPN 610 620 YLQNVLAELA AQGVTEDCLE QQ
	Isoform 2 (B) [UniParc]. Checksum: 449202FB53C026B3	FASTA	575	62,344
	10 20 30 40 50 60 MAMAPSPSLV QVYTSPAAVA VWEWQDGLGT WHPYSATVCS FIEQQFVQQK GQRFGLGSLA 70 80 90 100 110 120 HSIPLGQADP SLAPYIIDLP SWTQFRQDTG TMRAVRRHLF PQHSAPGRGV VWEWLSDDGS 130 140 150 160 170 180 WTAYEASVCD YLEQQVARGN QLVDLAPLGY NYTVNYTTHT QTNKTSSFCR SVRRQAGPPY 190 200 210 220 230 240 PVTTIIAPPG HTGVACSCHQ CLSGSRTGPV SGRYRHSMTN LPAYPVPQHP PHRTASVFGT 250 260 270 280 290 300 HQAFAPYNKP SLSGARSAPR LNTTNAWGAA PPSLGSQPLY RSSLSHLGPQ HLPPGSSTSG 310 320 330 340 350 360 AVSASLPSGP SSSPGSVPAT VPMQMPKPSR VQQALAGATP KPEPEPEQVI KNYTEELKVP 370 380 390 400 410 420 PDEDCIICME KLSTASGYSD VTDSKAIGSL AVGHLTKCSH AFHLLCLLAM YCNGNKDGSL 430 440 450 460 470 480 QCPSCKTIYG EKTGTQPQGK MEVLRFQMSL PGHEDCGTIL IVYSIPHGIQ GPEHPNPGKP 490 500 510 520 530 540 FTARGFPRQC YLPDNAQGRK VLELLKVAWK RRLIFTVGTS STTGETDTVV WNEIHHKTEM 550 560 570 DRNITGHGYP DPNYLQNVLA ELAAQGVTED CLEQQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity." Takeyama K., Aguiar R.C.T., Gu L., He C., Freeman G.J., Kutok J.L., Aster J.C., Shipp M.A. J. Biol. Chem. 278:21930-21937(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), VARIANT GLU-384, SUBUNIT, IN VITRO UBIQUITIN LIGASE ACTIVITY.
[2]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLU-384 AND ALA-421. Tissue: Brain.
[3]	"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] (ISOFORM 1), VARIANT ALA-421. Tissue: Thyroid.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 1), VARIANT GLU-384. Tissue: Brain, Lymph and Muscle.
[6]	"Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor." Yamamoto N., Yamamoto S., Inagaki F., Kawaichi M., Fukamizu A., Kishi N., Matsuno K., Nakamura K., Weinmaster G., Okano H., Nakafuku M. J. Biol. Chem. 276:45031-45040(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY225124 mRNA. Translation: AAP57518.1. AY225125 mRNA. Translation: AAP57519.1. AB040961 mRNA. Translation: BAA96052.1. Different initiation. AK023924 mRNA. Translation: BAB14727.1. AC005522 Genomic DNA. Translation: AAP21881.1. AC007078 Genomic DNA. No translation available. BC008856 mRNA. Translation: AAH08856.1. BC018555 mRNA. Translation: AAH18555.1. BC026059 mRNA. Translation: AAH26059.1. BC093079 mRNA. Translation: AAH93079.1.
IPI	IPI00292746. IPI00377117.
RefSeq	NP_001096064.1. NM_001102594.1. NP_001096065.1. NM_001102595.1. NP_001096066.1. NM_001102596.1. NP_065943.2. NM_020892.2.
UniGene	Hs.187058.
3D structure databases
ProteinModelPortal	Q86UW9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q86UW9. 12 interactions.
MINT	MINT-1436106.
STRING	9606.ENSP00000322885.
PTM databases
PhosphoSite	Q86UW9.
Polymorphism databases
DMDM	68067880.
Proteomic databases
PaxDb	Q86UW9.
PRIDE	Q86UW9.
Protocols and materials databases
DNASU	113878.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307569; ENSP00000305242; ENSG00000091073. ENST00000324432; ENSP00000322885; ENSG00000091073. ENST00000413936; ENSP00000390218; ENSG00000091073. ENST00000430490; ENSP00000411986; ENSG00000091073. ENST00000446820; ENSP00000392545; ENSG00000091073.
GeneID	113878.
KEGG	hsa:113878.
UCSC	uc003uff.4. human. uc003ufj.4. human.
Organism-specific databases
CTD	113878.
GeneCards	GC07P076090.
HGNC	HGNC:15973. DTX2.
HPA	HPA042931.
MIM	613141. gene.
neXtProt	NX_Q86UW9.
PharmGKB	PA27515.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0323.
HOGENOM	HOG000007352.
HOVERGEN	HBG007213.
InParanoid	Q86UW9.
KO	K06058.
OMA	YPVTTVI.
OrthoDB	EOG4XSKPV.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q86UW9.
Bgee	Q86UW9.
CleanEx	HS_DTX2.
Genevestigator	Q86UW9.
GermOnline	ENSG00000091073. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR004170. WWE-dom. IPR018123. WWE-dom_subgr. IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF02825. WWE. 2 hits. PF00097. zf-C3HC4. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. SM00678. WWE. 2 hits. [Graphical view]
PROSITE	PS50918. WWE. 2 hits. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DTX2. human.
GenomeRNAi	113878.
NextBio	78930.
SOURCE	Search...

Entry information

Entry name

DTX2_HUMAN

Accession

Primary (citable) accession number: Q86UW9
Secondary accession number(s): Q6XM87 , Q6XM88, Q96H69, Q9H890, Q9P200

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	June 21, 2005
Last modified:	May 1, 2013
This is version 99 of the entry and version 3 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.