Reviewed, UniProtKB/Swiss-Prot Q960X8 (HRS_DROME)

Names and origin

Protein names

Recommended name:
    Hepatocyte growth factor-regulated tyrosine kinase substrate

Gene names

Name:	Hrs
ORF Names:	CG2903

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	760 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Essential role in endosome membrane invagination and formation of multivesicular bodies, MVBs. Required during gastrulation and appears to regulate early embryonic signaling pathways. Inhibits tyrosine kinase receptor signaling by promoting degradation of the tyrosine-phosphorylated, active receptor, potentially by sorting activated receptors into MVBs. The MVBs are then trafficked to the lysosome where their contents are degraded. Ref.1
Subunit structure	Homodimer; in vitro. Interacts with ubiquitin. Ref.1 Ref.6
Subcellular location	Cytoplasm › cell cortex. Cytoplasm › perinuclear region. Note: Locates to vesicles present in the perinuclear regions of muscle cells and in the periphery of Garland cells of third-instar larvae. Ref.1
Developmental stage	Expressed both maternally and zygotically throughout development. Ref.1
Sequence similarities	Contains 1 FYVE-type zinc finger. Contains 1 UIM (ubiquitin-interacting motif) repeat. Contains 1 VHS domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	border follicle cell migration Inferred from mutant phenotype. Source: FlyBase endocytosis Inferred from mutant phenotype. Source: FlyBase endosome transport Traceable author statement. Source: FlyBase intracellular protein transport Inferred from electronic annotation. Source: InterPro multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of epidermal growth factor receptor signaling pathway Non-traceable author statement. Source: FlyBase synaptic vesicle priming Non-traceable author statement. Source: FlyBase torso signaling pathway Non-traceable author statement. Source: FlyBase vesicle organization Non-traceable author statement. Source: FlyBase
Cellular component	cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Traceable author statement. Source: FlyBase perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle Non-traceable author statement. Source: FlyBase
Molecular function	protein binding Ref.1 Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Cog7	Q9VAD6	1	EBI-90175,EBI-105290
lmg	Q9VLJ5	1	EBI-90175,EBI-130492
RpL40	P68198	1	EBI-90175,EBI-86340
Stam	Q9XTL2	1	EBI-90175,EBI-87548

Alternative products

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

Isoform B (identifier: Q960X8-1)

Also known as: C;

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 A (identifier: Q960X8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MFRSSFDKNLENAT → MSSEEELSIEEESL
     15-127: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 760

760

Hepatocyte growth factor-regulated tyrosine kinase substrate

PRO_0000084070

Regions

Domain

13 – 141

129

VHS

Repeat

263 – 282

20

UIM

Zinc finger

158 – 218

61

FYVE-type

Compositional bias

439 – 745

307

Gln/Pro-rich

Amino acid modifications

Modified residue

300

1

Phosphoserine Ref.5

Modified residue

302

1

Phosphoserine Ref.5

Natural variations

Alternative sequence

1 – 14

14

MFRSS…LENAT → MSSEEELSIEEESL in isoform A.

VSP_029168

Alternative sequence

15 – 127

113

Missing in isoform A.

VSP_029169

Experimental info

Sequence conflict

471

1

E → G in AAN71346. Ref.4

Secondary structure

1

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760

Helix Strand Turn

Details...

Helix

5 – 14

10

Helix

23 – 34

12

Helix

40 – 51

12

Helix

56 – 72

17

Helix

74 – 81

8

Helix

84 – 96

13

Helix

100 – 116

17

Turn

117 – 119

3

Helix

125 – 135

11

Turn

165 – 167

3

Beta strand

173 – 175

3

Turn

181 – 183

3

Beta strand

194 – 198

5

Helix

199 – 201

3

Beta strand

203 – 209

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform B (C) [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 993833378D094F2C	FASTA	760	85,415
	10 20 30 40 50 60 MFRSSFDKNL ENATSHLRLE PDWPSILLIC DEINQKDVTP KNAFAAIKKK MNSPNPHSSC 70 80 90 100 110 120 YSLLVLESIV KNCGAPVHEE VFTKENCEMF SSFLESTPHE NVRQKMLELV QTWAYAFRSS 130 140 150 160 170 180 DKYQAIKDTM TILKAKGHTF PELREADAMF TADTAPNWAD GRVCHRCRVE FTFTNRKHHC 190 200 210 220 230 240 RNCGQVFCGQ CTAKQCPLPK YGIEKEVRVC DGCFAALQRP TSGSGGAKSG PRPADSELPA 250 260 270 280 290 300 EYLNSTLAQQ VQTPARKTEQ ELKEEEELQL ALALSQSEAE QQKPKLQSLP PAAYRMQQRS 310 320 330 340 350 360 PSPEAPPEPK EYHQQPEEAT NPELAKYLNR SYWEQRKISE SSSMASPSAP SPMPPTPQPQ 370 380 390 400 410 420 QIMPLQVKSA DEVQIDEFAA NMRTQVEIFV NRMKSNSSRG RSISNDSSVQ TLFMTLTSLH 430 440 450 460 470 480 SQQLSYIKEM DDKRMWYEQL QDKLTQIKDS RAALDQLRQE HVEKLRRIAE EQERQRQMQM 490 500 510 520 530 540 AQKLDIMRKK KQEYLQYQRQ LALQRIQEQE REMQLRQEQQ KAQYLMGQSA PPFPYMPPSA 550 560 570 580 590 600 VPQHGSPSHQ LNNVYNPYAA GVPGYLPQGP APAPNGHGQF QAIPPGMYNP AIQQPMPPNL 610 620 630 640 650 660 QPGGLMQQPA PPGNPQMMPP MPENQFANNP AAILQLPQQH SIAQPPQIPF QPQPQQIPGQ 670 680 690 700 710 720 QPQQIPGQQP QQIPGQQPQQ IPGQQPQQIP VQQPQPQPQM GHVMLQQHQA PPAAQAPPVT 730 740 750 760 EIANNQVQAV AAAPAPPQNE PGPAPVKAEE PATAELISFD
	Isoform A. Checksum: 40A42C2796C736B3	FASTA	647	72,413
	10 20 30 40 50 60 MSSEEELSIE EESLDTMTIL KAKGHTFPEL READAMFTAD TAPNWADGRV CHRCRVEFTF 70 80 90 100 110 120 TNRKHHCRNC GQVFCGQCTA KQCPLPKYGI EKEVRVCDGC FAALQRPTSG SGGAKSGPRP 130 140 150 160 170 180 ADSELPAEYL NSTLAQQVQT PARKTEQELK EEEELQLALA LSQSEAEQQK PKLQSLPPAA 190 200 210 220 230 240 YRMQQRSPSP EAPPEPKEYH QQPEEATNPE LAKYLNRSYW EQRKISESSS MASPSAPSPM 250 260 270 280 290 300 PPTPQPQQIM PLQVKSADEV QIDEFAANMR TQVEIFVNRM KSNSSRGRSI SNDSSVQTLF 310 320 330 340 350 360 MTLTSLHSQQ LSYIKEMDDK RMWYEQLQDK LTQIKDSRAA LDQLRQEHVE KLRRIAEEQE 370 380 390 400 410 420 RQRQMQMAQK LDIMRKKKQE YLQYQRQLAL QRIQEQEREM QLRQEQQKAQ YLMGQSAPPF 430 440 450 460 470 480 PYMPPSAVPQ HGSPSHQLNN VYNPYAAGVP GYLPQGPAPA PNGHGQFQAI PPGMYNPAIQ 490 500 510 520 530 540 QPMPPNLQPG GLMQQPAPPG NPQMMPPMPE NQFANNPAAI LQLPQQHSIA QPPQIPFQPQ 550 560 570 580 590 600 PQQIPGQQPQ QIPGQQPQQI PGQQPQQIPG QQPQQIPVQQ PQPQPQMGHV MLQQHQAPPA 610 620 630 640 AQAPPVTEIA NNQVQAVAAA PAPPQNEPGP APVKAEEPAT AELISFD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila." Lloyd T.E., Atkinson R., Wu M.N., Zhou Y., Pennetta G., Bellen H.J. Cell 108:261-269(2002) [PubMed: 11832215] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INTERACTION WITH UBI-P63E. Strain: Berkeley. Tissue: Embryo.
[2]	"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.
[3]	"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, ALTERNATIVE SPLICING.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Strain: Berkeley. Tissue: Embryo.
[5]	"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-300 AND SER-302, MASS SPECTROMETRY. Tissue: Embryo.
[6]	"Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction." Mao Y., Nickitenko A., Duan X., Lloyd T.E., Wu M.N., Bellen H., Quiocho F.A. Cell 100:447-456(2000) [PubMed: 10693761] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), HOMODIMERIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AY071846 mRNA. Translation: AAL60055.1.
AE014134 Genomic DNA. Translation: AAF51221.2.
AE014134 Genomic DNA. Translation: AAF51222.1.
AE014134 Genomic DNA. Translation: AAN10412.2.
AY051789 mRNA. Translation: AAK93213.1.
BT001591 mRNA. Translation: AAN71346.1.

RefSeq

NP_525099.3.
NP_722830.2.
NP_722831.1.

UniGene

Dm.274

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DVP	X-ray	2.00	A	1-219	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q960X8. 43 interactions.

Proteomic databases

PRIDE

Q960X8.

Genome annotation databases

Ensembl

FBgn0031450. Drosophila melanogaster. [Contig view]

GeneID

33458.

KEGG

dme:Dmel_CG2903.

Organism-specific databases

FlyBase

FBgn0031450. Hrs.

Phylogenomic databases

HOGENOM

Q960X8.

OMA

Q960X8. FQSINNM.

Enzyme and pathway databases

BioCyc

DMEL-XXX-02:DMEL-XXX-02-007044-MON.
DMEL-XXX-02:DMEL-XXX-02-007045-MON.

Gene expression databases

ArrayExpress

Q960X8.

GermOnline

CG2903. Drosophila melanogaster.

Family and domain databases

InterPro

IPR008942. ENTH_VHS.
IPR017073. Ubi_bd_Hrs_VPS27.
IPR003903. Ubiquitin-int_motif.
IPR002014. VHS.
IPR018205. VHS_subgroup.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
[Graphical view]

Gene3D

G3DSA:1.25.40.90. ENTH_VHS. 1 hit.

Pfam

PF01363. FYVE. 1 hit.
PF02809. UIM. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]

PIRSF

PIRSF036956. Hrs_Vps27. 1 hit.

ProDom

PD003686. VHS. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00064. FYVE. 1 hit.
SM00726. UIM. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]

PROSITE

PS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

783669.

Entry information

Entry name

HRS_DROME

Accession

Primary (citable) accession number: Q960X8
Secondary accession number(s): A4V018 , Q8IGU6, Q9VQF2, Q9VQF3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project