Reviewed, UniProtKB/Swiss-Prot P51592 (HYD_DROME)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase hyd
    EC=6.3.2.-
Alternative name(s):
    Protein hyperplastic discs

Gene names

Name:	hyd
Synonyms:	l(3)C43
ORF Names:	CG9484

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	2885 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates By similarity. Required for regulation of cell proliferation in imaginal disks and germ cells. Acts as a negative regulator of hh, ci and dpp expression in the anterior of the eye disk. Ref.1 Ref.5
Subcellular location	Nucleus Potential.
Developmental stage	Expressed at all stages of development, with high levels at the embryonic and pupal stages (at protein level). Ref.1
Disruption phenotype	Ectopic expression of hh and dpp, resulting in non autonomous overgrowth of the disc and premature photoreceptor differentiation that propagates into the surrounding tissue. Ref.1
Miscellaneous	A cysteine residue is required for ubiquitin-thioester formation.
Sequence similarities	Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 1 PABC domain. Contains 1 UBA domain. Contains 1 UBR-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	compound eye development Non-traceable author statement. Source: FlyBase eye-antennal disc morphogenesis Ref.5 Inferred from mutant phenotype. Source: FlyBase female gonad development Inferred from mutant phenotype. Source: FlyBase imaginal disc growth Ref.1 Inferred from mutant phenotype. Source: FlyBase modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of smoothened signaling pathway Non-traceable author statement. Source: FlyBase protein modification process Inferred from electronic annotation. Source: InterPro regulation of proteolysis Non-traceable author statement. Source: FlyBase spermatogenesis Ref.1 Inferred from mutant phenotype. Source: FlyBase
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: FlyBase nucleus Ref.1 Inferred from direct assay. Source: FlyBase
Molecular function	RNA binding Inferred from electronic annotation. Source: InterPro ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2885	2885	E3 ubiquitin-protein ligase hyd		PRO_0000084107
Regions
	Domain	154 – 196	43	UBA
	Domain	2484 – 2561	78	PABC
	Domain	2782 – 2885	104	HECT
	Zinc finger	1217 – 1285	69	UBR-type
	Compositional bias	962 – 1112	151	Ser-rich
Sites
	Active site	2854	1	Glycyl thioester intermediate By similarity
Amino acid modifications
	Modified residue	628	1	Phosphoserine Ref.7
	Modified residue	631	1	Phosphoserine Ref.7
	Modified residue	967	1	Phosphoserine Ref.7
	Modified residue	1362	1	Phosphoserine Ref.7
	Modified residue	2037	1	Phosphoserine Ref.7
	Modified residue	2183	1	Phosphoserine Ref.6
	Modified residue	2574	1	Phosphoserine Ref.7
Experimental info
	Sequence conflict	125	1	T → A in AAB88625. Ref.1
	Sequence conflict	277	1	T → A in AAB88625. Ref.1
	Sequence conflict	294	1	S → P in AAB88625. Ref.1
	Sequence conflict	377	1	S → A in AAB88625. Ref.1
	Sequence conflict	383	1	Y → C in AAB88625. Ref.1
	Sequence conflict	386	1	R → G in AAB88625. Ref.1
	Sequence conflict	397	1	T → A in AAB88625. Ref.1
	Sequence conflict	407	1	S → C in AAB88625. Ref.1
	Sequence conflict	657	1	A → G in AAB88625. Ref.1
	Sequence conflict	741 – 759	19	EDVQI…PDWLQ → KMSDISHCYVTRLLA in AAB88625. Ref.1
	Sequence conflict	1490	1	V → A in AAB88625. Ref.1
	Sequence conflict	1497	1	E → Q in AAB88625. Ref.1
	Sequence conflict	1503 – 1505	3	EKR → QKQ in AAB88625. Ref.1
	Sequence conflict	1557 – 1559	3	MSS → CHR in AAB88625. Ref.1
	Sequence conflict	1625	1	R → G in AAB88625. Ref.1
	Sequence conflict	1641	1	R → G in AAB88625. Ref.1
	Sequence conflict	1784	1	P → R in AAB88625. Ref.1
	Sequence conflict	1978	1	T → S in AAB88625. Ref.1
	Sequence conflict	2037	1	S → T in AAB88625. Ref.1
	Sequence conflict	2096	1	G → A in AAB88625. Ref.1
	Sequence conflict	2167	1	G → GELRVYAVNNLQTLNFQSTR in AAB88625. Ref.1
	Sequence conflict	2239 – 2272	34	SASNL…ARGSQ → RLQIYRPQNKPNVIHNIKSQ HQTTCYYFLLVVLS Ref.1
	Sequence conflict	2280 – 2284	5	ELPSW → GIAPC in AAB88625. Ref.1
	Sequence conflict	2290 – 2291	2	RW → A in AAB88625. Ref.1
	Sequence conflict	2301	1	V → P in AAB88625. Ref.1
	Sequence conflict	2439 – 2440	2	SR → T in AAB88625. Ref.1
	Sequence conflict	2601	1	T → I in AAB88625. Ref.1
	Sequence conflict	2646	1	G → R in AAB88625. Ref.1
	Sequence conflict	2711 – 2728	18	AVTSS…YTEYR → VSHRVIYSSTSDAIQNID in AAB88625. Ref.1
	Sequence conflict	2814	1	D → H in AAB88625. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P51592-1 [UniParc]. Last modified July 5, 2005. Version 3. Checksum: F0735C28C962F85E	FASTA	2,885	318,881
	10 20 30 40 50 60 MVSMQFVLQP LPGSDDQFIE RIREVSDKVN RFGYGSHRIF EQLKIPVKEV VIGPAHIGVL 70 80 90 100 110 120 LEDGKAFRVS FSINSEKLDL TKSDAKCSTS GGSGTASASK APSSSRPMAR SRARLLRATG 130 140 150 160 170 180 RSNSTGQGSG SRSTGVIIGG STSSRPLVTV PATYVPEELI SQAEVVLQGK SRNLIIRELQ 190 200 210 220 230 240 RTNLDVNLAV NNLLSRDDEE AEDTEEGADN YVPEDLISLL DNGFSGDNNS VIIDPSDGLF 250 260 270 280 290 300 SEEIFSNYSS IRNLLFDRIR SERSNANANA ADSNQSTTRS TSSGTALTGN SGLSAQISVN 310 320 330 340 350 360 ADREAFSRWR DRQYYGPRRW ISKDDYTWEK DADSKKKEPS PMLSPIWISE ELQPWPEKSS 370 380 390 400 410 420 VRFKTIGALY SEFIALSESG DLYQWRWSDA EPYKSETENV YHPKTVSLNI VERVELISAN 430 440 450 460 470 480 FIRCSVVTET NRVATWMDEQ LGYIGAKLEH SCCAFNEFIS DSITKIYVCS LYTVVKTESN 490 500 510 520 530 540 NIYWWGVLPF DQRRFLWDKF RTKTKKPFKV VATDINVGAQ VIMKKCPMYQ SGSIGFTCSN 550 560 570 580 590 600 GVPKVGQLLN SVWTFTDVCR MKIININTNS GVDKSQAAGN NLNAHGITPD KDLPKSTAMP 610 620 630 640 650 660 STGSSKNGQS FSNSKESTDR IDMPPPPSPA SSTCSDTGSV TSHKRTKRAT TKEDSNAPQE 670 680 690 700 710 720 GRKDEELWEV KDVVFVEDKV GPVGKVLKVD GDFVAVRFPA INAAAVAAAA AATSSTSNTA 730 740 750 760 770 780 STSKEEGKED DWQQCRLLRR EDVQIFRTAM STRGPDWLQK QPKKINVGGD AAGAQILTLA 790 800 810 820 830 840 VDSRGIHVIK KVLGKIHYSL YNLYNCKQEQ NCLFPTDCNS FIGSTPGNIL MACNDDCSGN 850 860 870 880 890 900 SSTIVLRDGN GALYPLAKDC LGSIKDPQWF DLPPVKSITM STISLPAMLS GVNLKSKVCM 910 920 930 940 950 960 TALLFDTQKL MPHILRCDVK NSFAALGRLE REDQADTALV VEERCDGARN IFHACVIMCA 970 980 990 1000 1010 1020 PSSNKDSPPD SPSGGVEKKS LVGLSVARSI PTVSTSAYVS SIAFGASASS SNENSSFATM 1030 1040 1050 1060 1070 1080 SSSAAGSASS TSRDNRTNLR DMMNRLINSD QAEQSGSQPM ATNNEDHAYI PWPAETPAAS 1090 1100 1110 1120 1130 1140 NLSASSSQNV SDSIEDDISK IIPSSSQSSM LSNIKLGSPT YTFDLAQRRE HALTILQQMC 1150 1160 1170 1180 1190 1200 VSPALRPYLC HMLSTKDAQG QTPFMLSVSC RAYEAGIILL NTILMLSEQD PQLKEAMIFP 1210 1220 1230 1240 1250 1260 NGSPADQSPL HVICYNDTCS FTWTGADHIN QNIFECKTCG LTGSLCCCTE CARVCHKGHD 1270 1280 1290 1300 1310 1320 CKLKRTAPTA YCDCWEKCKC KALIAGNLTK RFALLCKLVS CTDLVTKFNS KGESILLFLI 1330 1340 1350 1360 1370 1380 QTVGRQIVEQ RQYRFSVRVR NVSTAATGAT GNNSVISNRK TSAAEIDNDM PDHDLEPPKF 1390 1400 1410 1420 1430 1440 ARKALERLLI DWNAVRSMIM SGAERGDVPN PAGSASENSN SEGFNMFIQT QHGSTLLDKF 1450 1460 1470 1480 1490 1500 THSLIVKCTS DHLDTLLLTL VRELQNASVS NRSKEAEEVV RRFVRSVARV FVIFNLEKQP 1510 1520 1530 1540 1550 1560 NPEKRKSHSS CNKYVQSCVK VFQTLHKISI EELCEVSEAL IAPVRLGVVR PTAPFTMSSS 1570 1580 1590 1600 1610 1620 NLDNSDDLFS VDPLAPSNVE SPSEQILVHD AGNDQSANFN IQQNYDVVAM ETIRDASESE 1630 1640 1650 1660 1670 1680 EVINREANSH NQDDELIENQ RNEDGMQDDE SDNDFTFNDA ETESDSDDNQ SNQEVQRSVQ 1690 1700 1710 1720 1730 1740 AGATVGSEND IGVLFLEDES GDSSAQEEDG SEDGESDDQS DEFNFNEQQL ERRSTNSNAR 1750 1760 1770 1780 1790 1800 SDLAPQTMQW AIRSRDTARS SVRVPTGSNM VFIDPMALRR STVPASTTVT TPSIEPHTMA 1810 1820 1830 1840 1850 1860 TTASNLARAF GITIRQISEL ISILSYNVLN DIETSLKIQN DEAIAVQAFV EKRLKATWDW 1870 1880 1890 1900 1910 1920 MFTVMDGTEA QLKFGAYLTN YTDPNHPLHP LNLSAQASSS QTPAPATSSS VNGVNIMGSN 1930 1940 1950 1960 1970 1980 SRRDFFTYCL SLMRSHTSEH RDALPVLDIT ALRHIAYVLD AFVYYMRNDS GFYDKQDTIS 1990 2000 2010 2020 2030 2040 GRINNLSPMT ESYDTDDELA NLEEFNADVQ MSASSMPSGS QGTRRHAFFA RSESTLSLGC 2050 2060 2070 2080 2090 2100 SAPEGFELPL DMAMPLADKP HLLQPNSKRQ ELFANLPLLV TTNANNSGAT NDGDGGSIFD 2110 2120 2130 2140 2150 2160 YTPTRLGFSN SLKRNERVYE TVPIDSSKTG DGNVTNKAEG STDSNIYVQL KKKQGSDDFK 2170 2180 2190 2200 2210 2220 SHKEADGNQS KYEKVVLMET DDSLPSTSKS TEALMATRPE VIIAPNKASV SPATAARSVI 2230 2240 2250 2260 2270 2280 VLAGGSCLKT IDSDINNYSA SNLSTAEQAK CDTQYQKSTS DHLLLFPARG SQFYQSNFSE 2290 2300 2310 2320 2330 2340 LPSWNFLLSR WKLTLDLFGR VFMDDVGMEH GSVLPELRGF PVKEMRFRRH MEKLRNGQQR 2350 2360 2370 2380 2390 2400 DLVLCKLERN RESLIVQTFK ELNTQFGNQS RRIQPPITFN RVKVTFKDEP GEGSGVARSF 2410 2420 2430 2440 2450 2460 YTSIAEALLA SAKIPNLESV QVGTNHSKYV VPFSSILRSR TVSGSSRDQS TLQRRGSNSK 2470 2480 2490 2500 2510 2520 ILWRSARERK ALNLDARPYT PPNSSDNATP ESLNDHLSVH LQQIGERLYP KIHSINQTHA 2530 2540 2550 2560 2570 2580 PKITGMLLEI PTPQLLSVIS SDETLRQKVN EAIEIITFKQ KSETSAQSSQ PKKSPSVVVV 2590 2600 2610 2620 2630 2640 DPVDDDNEPL FYSPGKRGFY TPRQGFASFE RINAFRNIGR LIGLCLLQNE LLPLFLQRHV 2650 2660 2670 2680 2690 2700 LKYILGRKIK FHDLAFFDPA LYESFRQIIQ NAQTKEGEET INRMELCFVI DLMKEEGCGN 2710 2720 2730 2740 2750 2760 RELIPGGRDV AVTSSNIFEY VRRYTEYRLI KSQEKALEAL KDGVFDVLPD NSMINLTAED 2770 2780 2790 2800 2810 2820 LRLLLNGVGD INVSTLISYT TFNDESSEGP DKLLKFKKWF WSIVEKMNIM ERQDLVYFWT 2830 2840 2850 2860 2870 2880 GSPALPASEE GFQPLPSVTI RPADDSHLPT ANTCISRLYI PLYSSKSILR SKMLMAIKSK NFGFV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genetic and molecular analysis of hyperplastic discs, a gene whose product is required for regulation of cell proliferation in Drosophila melanogaster imaginal discs and germ cells." Mansfield E., Hersperger E., Biggs J., Shearn A. Dev. Biol. 165:507-526(1994) [PubMed: 7958417] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[2]	Shearn A. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[5]	"The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms." Lee J.D., Amanai K., Shearn A., Treisman J.E. Development 129:5697-5706(2002) [PubMed: 12421709] [Abstract] Cited for: FUNCTION.
[6]	"An integrated chemical, mass spectrometric and computational strategy for (quantitative) phosphoproteomics: application to Drosophila melanogaster Kc167 cells." Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A., Eng J.K., Aebersold R., Tao W.A. Mol. Biosyst. 3:275-286(2007) [PubMed: 17372656] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2183, MASS SPECTROMETRY.
[7]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628; SER-631; SER-967; SER-1362; SER-2037 AND SER-2574, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L14644 mRNA. Translation: AAB88625.1. AE014297 Genomic DNA. Translation: AAF54431.2.
PIR	T08437.
RefSeq	NP_524296.2.
UniGene	Dm.7365
3D structure databases
SMR	P51592. Positions 150-198, 2499-2568, 2611-2878.
ModBase	Search...
Protein-protein interaction databases
STRING	P51592.
Genome annotation databases
Ensembl	FBtr0082090; FBpp0081568; FBgn0002431; Drosophila melanogaster. [Genome view]
GeneID	41181.
KEGG	dme:Dmel_CG9484.
NMPDR	fig|7227.3.peg.11948.
Organism-specific databases
CTD	41181.
FlyBase	FBgn0002431. hyd.
Phylogenomic databases
eggNOG	inNOG04787.
InParanoid	P51592.
OMA	MPYKRRR.
OrthoDB	EOG912MCX.
PhylomeDB	P51592.
Gene expression databases
GermOnline	CG9484. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000569. HECT. IPR002004. PABP_HYD. IPR009091. Reg_csome_cond/b-lactamase_inh. IPR015940. UBA/transl_elong_EF1B_N_euk. IPR003126. Znf_N-recognin. IPR013993. Znf_N-recognin_met. [Graphical view]
Gene3D	G3DSA:1.10.1900.10. PABP_HYD. 1 hit.
Pfam	PF00632. HECT. 1 hit. PF00658. PABP. 1 hit. PF02207. zf-UBR. 1 hit. [Graphical view]
SMART	SM00119. HECTc. 1 hit. SM00517. PolyA. 1 hit. SM00396. ZnF_UBR1. 1 hit. [Graphical view]
PROSITE	PS50237. HECT. 1 hit. PS51309. PABC. 1 hit. PS50030. UBA. 1 hit. PS51157. ZF_UBR. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	822597.

Entry information

Entry name

HYD_DROME

Accession

Primary (citable) accession number: P51592
Secondary accession number(s): Q9VH88

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 5, 2005
Last modified:	January 19, 2010
This is version 85 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project