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Protein

Hepatocyte growth factor-regulated tyrosine kinase substrate

Gene

Hrs

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Zinc fingeri158 – 218FYVE-typePROSITE-ProRule annotationCuratedAdd BLAST61

GO - Molecular functioni

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

GO - Biological processi

  • border follicle cell migration Source: FlyBase
  • early endosome to late endosome transport Source: FlyBase
  • endocytic recycling Source: FlyBase
  • endocytosis Source: FlyBase
  • endosomal 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 STAT protein import into nucleus Source: FlyBase
  • positive regulation of Toll signaling pathway Source: FlyBase
  • positive regulation of Wnt protein secretion Source: FlyBase
  • regulation of cell cycle Source: FlyBase
  • regulation of epidermal growth factor receptor signaling pathway 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

Keywordsi

Molecular functionDevelopmental protein
LigandMetal-binding, Zinc

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 lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2L

Organism-specific databases

FlyBaseiFBgn0031450 Hrs

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000840701 – 760Hepatocyte growth factor-regulated tyrosine kinase substrateAdd BLAST760

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei300Phosphoserine1 Publication1
Modified residuei302Phosphoserine1 Publication1

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

BgeeiFBgn0031450
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, 59 interactors
DIPiDIP-32844N
IntActiQ960X8, 45 interactors
STRINGi7227.FBpp0088692

Structurei

Secondary structure

1760
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 14Combined sources10
Helixi23 – 34Combined sources12
Helixi40 – 51Combined sources12
Helixi56 – 72Combined sources17
Helixi74 – 81Combined sources8
Helixi84 – 96Combined sources13
Helixi100 – 116Combined sources17
Turni117 – 119Combined sources3
Helixi125 – 135Combined sources11
Turni165 – 167Combined sources3
Beta strandi173 – 175Combined sources3
Turni181 – 183Combined sources3
Beta strandi194 – 198Combined sources5
Helixi199 – 201Combined sources3
Beta strandi203 – 209Combined sources7
Helixi211 – 219Combined sources9

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ960X8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 141VHSPROSITE-ProRule annotationCuratedAdd BLAST129
Domaini263 – 282UIMPROSITE-ProRule annotationAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi439 – 745Gln/Pro-richAdd BLAST307

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri158 – 218FYVE-typePROSITE-ProRule annotationCuratedAdd BLAST61

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1818 Eukaryota
ENOG410XNRF LUCA
GeneTreeiENSGT00670000098022
HOGENOMiHOG000021325
InParanoidiQ960X8
KOiK12182
OMAiYMYPAGA
OrthoDBiEOG091G06JJ
PhylomeDBiQ960X8

Family and domain databases

Gene3Di1.25.40.90, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR008942 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
PfamiView protein in Pfam
PF01363 FYVE, 1 hit
PF12210 Hrs_helical, 1 hit
PF00790 VHS, 1 hit
PIRSFiPIRSF036956 Hrs_Vps27, 1 hit
SMARTiView protein in SMART
SM00064 FYVE, 1 hit
SM00288 VHS, 1 hit
SUPFAMiSSF48464 SSF48464, 1 hit
SSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS50330 UIM, 1 hit
PS50179 VHS, 1 hit
PS50178 ZF_FYVE, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti471E → G in AAN71346 (PubMed:12537569).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0291681 – 14MFRSS…LENAT → MSSEEELSIEEESL in isoform A. CuratedAdd BLAST14
Alternative sequenceiVSP_02916915 – 127Missing in isoform A. CuratedAdd BLAST113

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

EnsemblMetazoaiFBtr0089749; FBpp0088690; FBgn0031450 [Q960X8-2]
FBtr0089750; FBpp0088691; FBgn0031450 [Q960X8-1]
FBtr0089751; FBpp0088692; FBgn0031450 [Q960X8-1]
GeneIDi33458
KEGGidme:Dmel_CG2903

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHRS_DROME
AccessioniPrimary (citable) accession number: Q960X8
Secondary accession number(s): A4V018
, Q8IGU6, Q9VQF2, Q9VQF3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: December 1, 2001
Last modified: March 28, 2018
This is version 146 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health