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Protein

Hepatocyte growth factor-regulated tyrosine kinase substrate

Gene

Hrs

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri158 – 21861FYVE-typePROSITE-ProRule annotationCuratedAdd
BLAST

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • ubiquitin binding Source: FlyBase

GO - Biological processi

  • border follicle cell migration Source: FlyBase
  • endocytosis Source: FlyBase
  • endosomal transport Source: FlyBase
  • endosome to lysosome transport Source: FlyBase
  • endosome transport via multivesicular body sorting pathway Source: FlyBase
  • exocytosis Source: FlyBase
  • exosomal secretion Source: FlyBase
  • intracellular protein transport Source: InterPro
  • membrane protein proteolysis Source: FlyBase
  • negative regulation of epidermal growth factor receptor signaling pathway Source: FlyBase
  • negative regulation of protein phosphorylation Source: FlyBase
  • neuron remodeling Source: FlyBase
  • neurotransmitter secretion Source: FlyBase
  • positive regulation of fibroblast growth factor receptor signaling pathway Source: FlyBase
  • positive regulation of protein ubiquitination Source: FlyBase
  • positive regulation of Toll signaling pathway Source: FlyBase
  • regulation of cell cycle Source: FlyBase
  • regulation of epithelial cell migration, open tracheal system Source: FlyBase
  • regulation of Notch signaling pathway Source: FlyBase
  • synaptic vesicle exocytosis Source: FlyBase
  • synaptic vesicle priming Source: FlyBase
  • torso signaling pathway Source: FlyBase
  • vesicle organization Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-DME-182971. EGFR downregulation.
R-DME-432720. Lysosome Vesicle Biogenesis.
R-DME-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor-regulated tyrosine kinase substrate
Gene namesi
Name:Hrs
ORF Names:CG2903
OrganismiDrosophila melanogaster (Fruit fly)Imported
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2L

Organism-specific databases

FlyBaseiFBgn0031450. Hrs.

Subcellular locationi

  • Cytoplasmcell cortex 1 Publication
  • Cytoplasmperinuclear region 1 Publication

  • Note: Locates to vesicles present in the perinuclear regions of muscle cells and in the periphery of Garland cells of third-instar larvae.

GO - Cellular componenti

  • cell cortex Source: UniProtKB-SubCell
  • cytoplasm Source: FlyBase
  • early endosome Source: FlyBase
  • endosome Source: FlyBase
  • ESCRT-0 complex Source: FlyBase
  • late endosome Source: FlyBase
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • synaptic vesicle Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 760760Hepatocyte growth factor-regulated tyrosine kinase substratePRO_0000084070Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei300 – 3001Phosphoserine1 Publication
Modified residuei302 – 3021Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ960X8.
PRIDEiQ960X8.

PTM databases

iPTMnetiQ960X8.

Expressioni

Developmental stagei

Expressed both maternally and zygotically throughout development.1 Publication

Gene expression databases

BgeeiQ960X8.
ExpressionAtlasiQ960X8. differential.
GenevisibleiQ960X8. DM.

Interactioni

Subunit structurei

Homodimer; in vitro. Interacts with ubiquitin.2 Publications

GO - Molecular functioni

  • ubiquitin binding Source: FlyBase

Protein-protein interaction databases

BioGridi59683. 42 interactions.
DIPiDIP-32844N.
IntActiQ960X8. 6 interactions.
MINTiMINT-331788.
STRINGi7227.FBpp0088692.

Structurei

Secondary structure

1
760
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi5 – 1410Combined sources
Helixi23 – 3412Combined sources
Helixi40 – 5112Combined sources
Helixi56 – 7217Combined sources
Helixi74 – 818Combined sources
Helixi84 – 9613Combined sources
Helixi100 – 11617Combined sources
Turni117 – 1193Combined sources
Helixi125 – 13511Combined sources
Turni165 – 1673Combined sources
Beta strandi173 – 1753Combined sources
Turni181 – 1833Combined sources
Beta strandi194 – 1985Combined sources
Helixi199 – 2013Combined sources
Beta strandi203 – 2097Combined sources
Helixi211 – 2199Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DVPX-ray2.00A1-219[»]
ProteinModelPortaliQ960X8.
SMRiQ960X8. Positions 1-219, 376-471.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ960X8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 141129VHSPROSITE-ProRule annotationCuratedAdd
BLAST
Domaini263 – 28220UIMPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi439 – 745307Gln/Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 FYVE-type zinc finger.PROSITE-ProRule annotationCurated
Contains 1 UIM (ubiquitin-interacting motif) domain.PROSITE-ProRule annotation
Contains 1 VHS domain.PROSITE-ProRule annotationCurated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri158 – 21861FYVE-typePROSITE-ProRule annotationCuratedAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1818. Eukaryota.
ENOG410XNRF. LUCA.
GeneTreeiENSGT00670000098022.
HOGENOMiHOG000021325.
InParanoidiQ960X8.
KOiK12182.
OMAiKRMWYEQ.
OrthoDBiEOG7N37CN.
PhylomeDBiQ960X8.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR008942. ENTH_VHS.
IPR024641. HRS_helical.
IPR017073. Ubi-bd_Hrs_VPS27.
IPR003903. UIM_dom.
IPR002014. VHS_dom.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF12210. Hrs_helical. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PIRSFiPIRSF036956. Hrs_Vps27. 1 hit.
SMARTiSM00064. FYVE. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF57903. SSF57903. 1 hit.
PROSITEiPS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B (identifier: Q960X8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MFRSSFDKNL ENATSHLRLE PDWPSILLIC DEINQKDVTP KNAFAAIKKK
60 70 80 90 100
MNSPNPHSSC YSLLVLESIV KNCGAPVHEE VFTKENCEMF SSFLESTPHE
110 120 130 140 150
NVRQKMLELV QTWAYAFRSS DKYQAIKDTM TILKAKGHTF PELREADAMF
160 170 180 190 200
TADTAPNWAD GRVCHRCRVE FTFTNRKHHC RNCGQVFCGQ CTAKQCPLPK
210 220 230 240 250
YGIEKEVRVC DGCFAALQRP TSGSGGAKSG PRPADSELPA EYLNSTLAQQ
260 270 280 290 300
VQTPARKTEQ ELKEEEELQL ALALSQSEAE QQKPKLQSLP PAAYRMQQRS
310 320 330 340 350
PSPEAPPEPK EYHQQPEEAT NPELAKYLNR SYWEQRKISE SSSMASPSAP
360 370 380 390 400
SPMPPTPQPQ QIMPLQVKSA DEVQIDEFAA NMRTQVEIFV NRMKSNSSRG
410 420 430 440 450
RSISNDSSVQ TLFMTLTSLH SQQLSYIKEM DDKRMWYEQL QDKLTQIKDS
460 470 480 490 500
RAALDQLRQE HVEKLRRIAE EQERQRQMQM AQKLDIMRKK KQEYLQYQRQ
510 520 530 540 550
LALQRIQEQE REMQLRQEQQ KAQYLMGQSA PPFPYMPPSA VPQHGSPSHQ
560 570 580 590 600
LNNVYNPYAA GVPGYLPQGP APAPNGHGQF QAIPPGMYNP AIQQPMPPNL
610 620 630 640 650
QPGGLMQQPA PPGNPQMMPP MPENQFANNP AAILQLPQQH SIAQPPQIPF
660 670 680 690 700
QPQPQQIPGQ QPQQIPGQQP QQIPGQQPQQ IPGQQPQQIP VQQPQPQPQM
710 720 730 740 750
GHVMLQQHQA PPAAQAPPVT EIANNQVQAV AAAPAPPQNE PGPAPVKAEE
760
PATAELISFD
Length:760
Mass (Da):85,415
Last modified:December 1, 2001 - v1
Checksum:i993833378D094F2C
GO
Isoform A (identifier: Q960X8-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:647
Mass (Da):72,413
Checksum:i40A42C2796C736B3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti471 – 4711E → G in AAN71346 (PubMed:12537569).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1414MFRSS…LENAT → MSSEEELSIEEESL in isoform A. CuratedVSP_029168Add
BLAST
Alternative sequencei15 – 127113Missing in isoform A. CuratedVSP_029169Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_525099.3. NM_080360.5. [Q960X8-1]
NP_722830.2. NM_164496.1. [Q960X8-1]
NP_722831.1. NM_164497.1. [Q960X8-2]
UniGeneiDm.274.

Genome annotation databases

EnsemblMetazoaiFBtr0089750; FBpp0088691; FBgn0031450. [Q960X8-1]
FBtr0089751; FBpp0088692; FBgn0031450. [Q960X8-1]
GeneIDi33458.
KEGGidme:Dmel_CG2903.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_525099.3. NM_080360.5. [Q960X8-1]
NP_722830.2. NM_164496.1. [Q960X8-1]
NP_722831.1. NM_164497.1. [Q960X8-2]
UniGeneiDm.274.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DVPX-ray2.00A1-219[»]
ProteinModelPortaliQ960X8.
SMRiQ960X8. Positions 1-219, 376-471.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi59683. 42 interactions.
DIPiDIP-32844N.
IntActiQ960X8. 6 interactions.
MINTiMINT-331788.
STRINGi7227.FBpp0088692.

PTM databases

iPTMnetiQ960X8.

Proteomic databases

PaxDbiQ960X8.
PRIDEiQ960X8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0089750; FBpp0088691; FBgn0031450. [Q960X8-1]
FBtr0089751; FBpp0088692; FBgn0031450. [Q960X8-1]
GeneIDi33458.
KEGGidme:Dmel_CG2903.

Organism-specific databases

CTDi33458.
FlyBaseiFBgn0031450. Hrs.

Phylogenomic databases

eggNOGiKOG1818. Eukaryota.
ENOG410XNRF. LUCA.
GeneTreeiENSGT00670000098022.
HOGENOMiHOG000021325.
InParanoidiQ960X8.
KOiK12182.
OMAiKRMWYEQ.
OrthoDBiEOG7N37CN.
PhylomeDBiQ960X8.

Enzyme and pathway databases

ReactomeiR-DME-182971. EGFR downregulation.
R-DME-432720. Lysosome Vesicle Biogenesis.
R-DME-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Miscellaneous databases

EvolutionaryTraceiQ960X8.
GenomeRNAii33458.
NextBioi783669.
PROiQ960X8.

Gene expression databases

BgeeiQ960X8.
ExpressionAtlasiQ960X8. differential.
GenevisibleiQ960X8. DM.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR008942. ENTH_VHS.
IPR024641. HRS_helical.
IPR017073. Ubi-bd_Hrs_VPS27.
IPR003903. UIM_dom.
IPR002014. VHS_dom.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF12210. Hrs_helical. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PIRSFiPIRSF036956. Hrs_Vps27. 1 hit.
SMARTiSM00064. FYVE. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF57903. SSF57903. 1 hit.
PROSITEiPS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Berkeley1 Publication.
  3. Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
    Strain: Berkeley.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
    Strain: Berkeley1 Publication.
    Tissue: Embryo1 Publication.
  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] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300 AND SER-302, IDENTIFICATION BY 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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), HOMODIMERIZATION.

Entry informationi

Entry nameiHRS_DROME
AccessioniPrimary (citable) accession number: Q960X8
Secondary accession number(s): A4V018
, Q8IGU6, Q9VQF2, Q9VQF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: December 1, 2001
Last modified: May 11, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.