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Protein

Lateral signaling target protein 2 homolog

Gene

ZFYVE28

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negative regulator of epidermal growth factor receptor (EGFR) signaling. Acts by promoting EGFR degradation in endosomes when not monoubiquitinated.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri817 – 879FYVE-typePROSITE-ProRule annotationAdd BLAST63

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • phosphatidylinositol-3-phosphate binding Source: UniProtKB

GO - Biological processi

  • negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • negative regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000159733-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Lateral signaling target protein 2 homolog
Short name:
hLst2
Alternative name(s):
Zinc finger FYVE domain-containing protein 28
Gene namesi
Name:ZFYVE28
Synonyms:KIAA1643, LST2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:29334. ZFYVE28.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • early endosome membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi87K → R: Abolishes monoubiquitination and promotes localization to early endosomes. 1 Publication1
Mutagenesisi823C → A: Abolishes binding to phosphatidylinositol 3-phosphate (PI3P). 1 Publication1

Organism-specific databases

DisGeNETi57732.
OpenTargetsiENSG00000159733.
PharmGKBiPA134904138.

Polymorphism and mutation databases

BioMutaiZFYVE28.
DMDMi251757462.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000987221 – 887Lateral signaling target protein 2 homologAdd BLAST887

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki87Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei334PhosphoserineCombined sources1
Modified residuei516PhosphothreonineCombined sources1
Modified residuei586Phosphoserine; by MAP2K1 Publication1
Modified residuei870Phosphothreonine; by MAP2K1 Publication1

Post-translational modificationi

Monoubiquitination at Lys-87 prevents binding to phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9HCC9.
PeptideAtlasiQ9HCC9.
PRIDEiQ9HCC9.

PTM databases

iPTMnetiQ9HCC9.
PhosphoSitePlusiQ9HCC9.

Expressioni

Gene expression databases

BgeeiENSG00000159733.
CleanExiHS_ZFYVE28.
ExpressionAtlasiQ9HCC9. baseline and differential.
GenevisibleiQ9HCC9. HS.

Organism-specific databases

HPAiHPA038175.
HPA057587.

Interactioni

Subunit structurei

Interacts with TRIM3.1 Publication

Protein-protein interaction databases

BioGridi121752. 7 interactors.
IntActiQ9HCC9. 1 interactor.
STRINGi9606.ENSP00000290974.

Structurei

3D structure databases

ProteinModelPortaliQ9HCC9.
SMRiQ9HCC9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The FYVE-type zinc finger mediates the interaction with phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes when not monoubiquitinated at Lys-87.1 Publication

Sequence similaritiesi

Belongs to the lst-2 family.Curated
Contains 1 FYVE-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri817 – 879FYVE-typePROSITE-ProRule annotationAdd BLAST63

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1819. Eukaryota.
ENOG410XNYQ. LUCA.
GeneTreeiENSGT00840000129741.
HOGENOMiHOG000185867.
InParanoidiQ9HCC9.
OMAiFGWAGST.
OrthoDBiEOG091G053Q.
PhylomeDBiQ9HCC9.
TreeFamiTF320752.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS50178. ZF_FYVE. 1 hit.
[Graphical view]

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HCC9-1) [UniParc]FASTAAdd to basket

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
MMNRFRKWLY KPKRSDPQLL ARFYYADEEL NQVAAELDSL DGRKDPQRCT
60 70 80 90 100
LLVSQFRSCQ DNVLNIINQI MDECIPQDRA PRDFCVKFPE EIRHDNLAGQ
110 120 130 140 150
LWFGAECLAA GSIIMNRELE SMAMRPLAKE LTRSLEDVRG ALRDQALRDL
160 170 180 190 200
NTYTEKMREA LRHFDVLFAE FELSYVSAMV PVKSPREYYV QQEVIVLFCE
210 220 230 240 250
TVERALDFGY LTQDMIDDYE PALMFSIPRL AIVCGLVVYA DGPLNLDRKV
260 270 280 290 300
EDMSELFRPF HTLLRKIRDL LQTLTEEELH TLERNLCISQ DVEFPIRADV
310 320 330 340 350
QGPAALAPAL SAPLPPEGPL SAKAKDPDAE LACSMQYDDQ ELEQLSRMVH
360 370 380 390 400
RAGDEMSSLL SPPIACQSPA HRPGAEGSPG GEASPGRPRL RSGSDEEERV
410 420 430 440 450
FFMDDVEGTA EALARPESPA GPFGWAGSTW ADPQEKGQGG PGGAAGISLP
460 470 480 490 500
ASEKEEDLSN NNLEAEGTDG ASLAGTSSCS CLDSRLHLDG WEVGADDAET
510 520 530 540 550
AEMIAHRTGG MKLSATVIFN PKSPTSLDSA VATQEAASEP VAEGMDGGPH
560 570 580 590 600
KLSTGATNCL LHSCVCCGSC GDSREDVVER LREKCSPGGV IGASYAAGLA
610 620 630 640 650
KASDRAPERQ EEAPPPSEDA SNGREPKAPT SDKCLPHTSG SQVDTASGLQ
660 670 680 690 700
GEAGVAGQQE PEARELHAGS PSAHEAPQAL SGSSSSTAGS CSSDKMGPEA
710 720 730 740 750
APAATHAAPQ ATREKIRSRF HGSHDLIHRL FVCISGVADQ LQTNYASDLR
760 770 780 790 800
SILKTLFEVM ATKPETDDKE KLRKVTQTLR SAALEDCALC QETLSSSELA
810 820 830 840 850
AKTRDGDFED PPEWVPDEAC GFCTACKAPF TVIRRKHHCR SCGKIFCSRC
860 870 880
SSHSAPLPRY GQVKPVRVCT HCYMFHVTPF YSDKAGL
Length:887
Mass (Da):96,490
Last modified:July 7, 2009 - v3
Checksum:iEAF3A26A50FF26F5
GO
Isoform 2 (identifier: Q9HCC9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     204-234: RALDFGYLTQDMIDDYEPALMFSIPRLAIVC → S

Note: No experimental confirmation available.
Show »
Length:857
Mass (Da):93,017
Checksum:iBC421651F2F690EF
GO
Isoform 3 (identifier: Q9HCC9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.

Note: No experimental confirmation available.
Show »
Length:817
Mass (Da):88,144
Checksum:iE37482D0F2C1797A
GO
Isoform 4 (identifier: Q9HCC9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.
     204-234: RALDFGYLTQDMIDDYEPALMFSIPRLAIVC → S

Note: No experimental confirmation available.
Show »
Length:787
Mass (Da):84,671
Checksum:i159ED7DEFBA6AD59
GO
Isoform 5 (identifier: Q9HCC9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-114: Missing.

Note: No experimental confirmation available.
Show »
Length:773
Mass (Da):83,198
Checksum:i18C28D3588B26C8D
GO
Isoform 6 (identifier: Q9HCC9-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     235-287: GLVVYADGPL...ELHTLERNLC → PLLPAHPRTR...LLRPLPELPP
     288-887: Missing.

Note: No experimental confirmation available.
Show »
Length:287
Mass (Da):32,724
Checksum:i282C75F9AD623A41
GO
Isoform 7 (identifier: Q9HCC9-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     14-60: Missing.
     205-219: ALDFGYLTQDMIDDY → NGKGVLKFMWNCNGP
     220-887: Missing.

Note: No experimental confirmation available.
Show »
Length:172
Mass (Da):20,170
Checksum:i03C358A6528554EA
GO
Isoform 8 (identifier: Q9HCC9-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.
     234-887: Missing.

Note: No experimental confirmation available.
Show »
Length:163
Mass (Da):18,907
Checksum:iF7B967E97FEEC3C4
GO

Sequence cautioni

The sequence AAH53664 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB13469 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti157M → I in BAG54362 (PubMed:14702039).Curated1
Sequence conflicti306L → P in BAH14855 (PubMed:14702039).Curated1
Sequence conflicti335M → I in BAH11855 (PubMed:14702039).Curated1
Sequence conflicti341E → G in BAG54362 (PubMed:14702039).Curated1
Sequence conflicti453E → D in BAH14855 (PubMed:14702039).Curated1
Sequence conflicti679A → G in BAG54362 (PubMed:14702039).Curated1
Sequence conflicti700A → P in BAH11855 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052988603S → N.1 PublicationCorresponds to variant rs17768776dbSNPEnsembl.1
Natural variantiVAR_052989672S → P.3 PublicationsCorresponds to variant rs661301dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0376141 – 114Missing in isoform 5. 1 PublicationAdd BLAST114
Alternative sequenceiVSP_0376151 – 70Missing in isoform 3, isoform 4 and isoform 8. 2 PublicationsAdd BLAST70
Alternative sequenceiVSP_04609214 – 60Missing in isoform 7. 1 PublicationAdd BLAST47
Alternative sequenceiVSP_037616204 – 234RALDF…LAIVC → S in isoform 2 and isoform 4. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_046093205 – 219ALDFG…MIDDY → NGKGVLKFMWNCNGP in isoform 7. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_046094220 – 887Missing in isoform 7. 1 PublicationAdd BLAST668
Alternative sequenceiVSP_046379234 – 887Missing in isoform 8. 1 PublicationAdd BLAST654
Alternative sequenceiVSP_045805235 – 287GLVVY…ERNLC → PLLPAHPRTRAGATAHVACR MVAGSSSGALTHPPVSKQGV ISALLRPLPELPP in isoform 6. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_045806288 – 887Missing in isoform 6. 1 PublicationAdd BLAST600

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046863 mRNA. Translation: BAB13469.1. Different initiation.
AK126692 mRNA. Translation: BAG54362.1.
AK293775 mRNA. Translation: BAH11593.1.
AK294710 mRNA. Translation: BAH11855.1.
AK294874 mRNA. Translation: BAH11908.1.
AK316484 mRNA. Translation: BAH14855.1.
AL158068 Genomic DNA. No translation available.
AL645924 Genomic DNA. No translation available.
BC032605 mRNA. No translation available.
BC035793 mRNA. No translation available.
BC053664 mRNA. Translation: AAH53664.1. Different initiation.
BC137309 mRNA. Translation: AAI37310.1.
BC137310 mRNA. Translation: AAI37311.1.
CCDSiCCDS33942.1. [Q9HCC9-1]
CCDS54708.1. [Q9HCC9-3]
CCDS54709.1. [Q9HCC9-8]
CCDS54710.1. [Q9HCC9-7]
CCDS54711.1. [Q9HCC9-2]
CCDS54712.1. [Q9HCC9-6]
RefSeqiNP_001166127.1. NM_001172656.1. [Q9HCC9-2]
NP_001166128.1. NM_001172657.1. [Q9HCC9-6]
NP_001166129.1. NM_001172658.1. [Q9HCC9-7]
NP_001166130.1. NM_001172659.1. [Q9HCC9-3]
NP_001166131.1. NM_001172660.1. [Q9HCC9-8]
NP_066023.2. NM_020972.2. [Q9HCC9-1]
XP_016863994.1. XM_017008505.1. [Q9HCC9-5]
UniGeneiHs.292056.

Genome annotation databases

EnsembliENST00000290974; ENSP00000290974; ENSG00000159733. [Q9HCC9-1]
ENST00000503000; ENSP00000423694; ENSG00000159733. [Q9HCC9-6]
ENST00000509171; ENSP00000422638; ENSG00000159733. [Q9HCC9-7]
ENST00000511071; ENSP00000425706; ENSG00000159733. [Q9HCC9-2]
ENST00000515169; ENSP00000425766; ENSG00000159733. [Q9HCC9-8]
ENST00000515312; ENSP00000426299; ENSG00000159733. [Q9HCC9-3]
GeneIDi57732.
KEGGihsa:57732.
UCSCiuc003gex.3. human. [Q9HCC9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046863 mRNA. Translation: BAB13469.1. Different initiation.
AK126692 mRNA. Translation: BAG54362.1.
AK293775 mRNA. Translation: BAH11593.1.
AK294710 mRNA. Translation: BAH11855.1.
AK294874 mRNA. Translation: BAH11908.1.
AK316484 mRNA. Translation: BAH14855.1.
AL158068 Genomic DNA. No translation available.
AL645924 Genomic DNA. No translation available.
BC032605 mRNA. No translation available.
BC035793 mRNA. No translation available.
BC053664 mRNA. Translation: AAH53664.1. Different initiation.
BC137309 mRNA. Translation: AAI37310.1.
BC137310 mRNA. Translation: AAI37311.1.
CCDSiCCDS33942.1. [Q9HCC9-1]
CCDS54708.1. [Q9HCC9-3]
CCDS54709.1. [Q9HCC9-8]
CCDS54710.1. [Q9HCC9-7]
CCDS54711.1. [Q9HCC9-2]
CCDS54712.1. [Q9HCC9-6]
RefSeqiNP_001166127.1. NM_001172656.1. [Q9HCC9-2]
NP_001166128.1. NM_001172657.1. [Q9HCC9-6]
NP_001166129.1. NM_001172658.1. [Q9HCC9-7]
NP_001166130.1. NM_001172659.1. [Q9HCC9-3]
NP_001166131.1. NM_001172660.1. [Q9HCC9-8]
NP_066023.2. NM_020972.2. [Q9HCC9-1]
XP_016863994.1. XM_017008505.1. [Q9HCC9-5]
UniGeneiHs.292056.

3D structure databases

ProteinModelPortaliQ9HCC9.
SMRiQ9HCC9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121752. 7 interactors.
IntActiQ9HCC9. 1 interactor.
STRINGi9606.ENSP00000290974.

PTM databases

iPTMnetiQ9HCC9.
PhosphoSitePlusiQ9HCC9.

Polymorphism and mutation databases

BioMutaiZFYVE28.
DMDMi251757462.

Proteomic databases

PaxDbiQ9HCC9.
PeptideAtlasiQ9HCC9.
PRIDEiQ9HCC9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000290974; ENSP00000290974; ENSG00000159733. [Q9HCC9-1]
ENST00000503000; ENSP00000423694; ENSG00000159733. [Q9HCC9-6]
ENST00000509171; ENSP00000422638; ENSG00000159733. [Q9HCC9-7]
ENST00000511071; ENSP00000425706; ENSG00000159733. [Q9HCC9-2]
ENST00000515169; ENSP00000425766; ENSG00000159733. [Q9HCC9-8]
ENST00000515312; ENSP00000426299; ENSG00000159733. [Q9HCC9-3]
GeneIDi57732.
KEGGihsa:57732.
UCSCiuc003gex.3. human. [Q9HCC9-1]

Organism-specific databases

CTDi57732.
DisGeNETi57732.
GeneCardsiZFYVE28.
HGNCiHGNC:29334. ZFYVE28.
HPAiHPA038175.
HPA057587.
MIMi614176. gene.
neXtProtiNX_Q9HCC9.
OpenTargetsiENSG00000159733.
PharmGKBiPA134904138.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1819. Eukaryota.
ENOG410XNYQ. LUCA.
GeneTreeiENSGT00840000129741.
HOGENOMiHOG000185867.
InParanoidiQ9HCC9.
OMAiFGWAGST.
OrthoDBiEOG091G053Q.
PhylomeDBiQ9HCC9.
TreeFamiTF320752.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000159733-MONOMER.

Miscellaneous databases

GenomeRNAii57732.
PROiQ9HCC9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159733.
CleanExiHS_ZFYVE28.
ExpressionAtlasiQ9HCC9. baseline and differential.
GenevisibleiQ9HCC9. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLST2_HUMAN
AccessioniPrimary (citable) accession number: Q9HCC9
Secondary accession number(s): B2RP83
, B3KX50, B7Z1Q7, B7Z2G9, B7Z2M2, B7ZB19, E9PB54, E9PB64, E9PG77, Q7Z6J3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: July 7, 2009
Last modified: November 2, 2016
This is version 116 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.