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Protein

Homer protein homolog 1

Gene

Homer1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 3 counteracts the effects by competing for binding sites. Isoform 1 regulates the trafficking and surface expression of GRM5. Isoform 3 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, and isoform 2 to regulate synaptic metabotropic glutamate function. Isoform 3, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development.1 Publication

GO - Molecular functioni

  • G-protein coupled glutamate receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein complex scaffold Source: BHF-UCL
  • protein heterodimerization activity Source: RGD
  • receptor binding Source: RGD
  • scaffold protein binding Source: BHF-UCL
  • type 5 metabotropic glutamate receptor binding Source: RGD

GO - Biological processi

  • circadian rhythm Source: RGD
  • G-protein coupled glutamate receptor signaling pathway Source: RGD
  • protein localization to synapse Source: BHF-UCL
  • response to cocaine Source: RGD
  • response to nicotine Source: RGD
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-6794361. Interactions of neurexins and neuroligins at synapses.

Names & Taxonomyi

Protein namesi
Recommended name:
Homer protein homolog 1
Alternative name(s):
PSD-Zip45
VASP/Ena-related gene up-regulated during seizure and LTP 1
Short name:
Vesl-1
Gene namesi
Name:Homer1
Synonyms:Homer, Vesl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi628725. Homer1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB-SubCell
  • dendrite Source: RGD
  • dendritic shaft Source: RGD
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • postsynaptic density Source: BHF-UCL
  • postsynaptic membrane Source: UniProtKB-KW
  • synapse Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24W → A: Disrupts binding to both GRM1 and SHANK3. 1 Publication1
Mutagenesisi24W → Y: Disrupts binding to GRM1. 1 Publication1
Mutagenesisi70T → A: Normal binding. 1 Publication1
Mutagenesisi70T → E: Disrupts binding to SHANK3. 1 Publication1
Mutagenesisi74F → A: Eliminates binding to both GRM1 and SHANK3. 1 Publication1
Mutagenesisi76Q → A: Normal binding. 1 Publication1
Mutagenesisi76Q → R: Normal binding. 1 Publication1
Mutagenesisi85V → A: Diminishes binding to GRM1. 1 Publication1
Mutagenesisi89G → A: Eliminates binding to both GRM1 and SHANK3. 1 Publication1
Mutagenesisi89G → N: Eliminates binding to both GRM1 and SHANK3. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001910071 – 366Homer protein homolog 1Add BLAST366

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei318PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z214.
PRIDEiQ9Z214.

PTM databases

iPTMnetiQ9Z214.
PhosphoSitePlusiQ9Z214.

Expressioni

Tissue specificityi

Highly expressed in cortex, Purkinje cells of the cerebellum, hippocampus, striatum and olfactory bulb. Isoform 1 and isoform 3 are expressed in skeletal and cardiac muscle.1 Publication

Developmental stagei

In the developing hippocampus, the expression of isoform 1 is high at P8, then decreased with progression of hippocampal development. Isoform 3 expression was constitutively low, and not regulated during hippocampal development.

Inductioni

Isoform 3 is induced in the hippocampus, by seizure and synaptic mechanisms in association with long-term potentiation (LTP). It is also induced in the striatum by drugs that alter dopamine signaling.

Gene expression databases

BgeeiENSRNOG00000047014.
ExpressionAtlasiQ9Z214. baseline and differential.
GenevisibleiQ9Z214. RN.

Interactioni

Subunit structurei

Interacts with GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. Interacts with IFT57 and OPHN1. Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Agap2Q8CGU44EBI-4410552,EBI-4409108
Grm5Q3UVX53EBI-4410552,EBI-8795045From a different organism.
Shank1Q9WV484EBI-2338999,EBI-80909

GO - Molecular functioni

  • G-protein coupled glutamate receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein complex scaffold Source: BHF-UCL
  • protein heterodimerization activity Source: RGD
  • receptor binding Source: RGD
  • scaffold protein binding Source: BHF-UCL
  • type 5 metabotropic glutamate receptor binding Source: RGD

Protein-protein interaction databases

BioGridi248180. 11 interactors.
IntActiQ9Z214. 9 interactors.
MINTiMINT-1891037.
STRINGi10116.ENSRNOP00000065989.

Structurei

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 16Combined sources14
Turni18 – 20Combined sources3
Beta strandi23 – 27Combined sources5
Beta strandi32 – 39Combined sources8
Turni40 – 43Combined sources4
Beta strandi44 – 51Combined sources8
Beta strandi54 – 60Combined sources7
Beta strandi71 – 79Combined sources9
Turni80 – 83Combined sources4
Beta strandi84 – 89Combined sources6
Helixi93 – 110Combined sources18
Helixi302 – 362Combined sources61

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DDVX-ray1.90A1-111[»]
1DDWX-ray1.70A1-120[»]
1I2HX-ray1.80A1-163[»]
3CVEX-ray1.75A/B/C/D302-366[»]
ProteinModelPortaliQ9Z214.
SMRiQ9Z214.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z214.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 110WH1PROSITE-ProRule annotationAdd BLAST110

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili193 – 364Sequence analysisAdd BLAST172

Domaini

The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3.

Sequence similaritiesi

Belongs to the Homer family.Curated
Contains 1 WH1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IGRQ. Eukaryota.
ENOG410XQWT. LUCA.
GeneTreeiENSGT00390000017850.
HOVERGENiHBG051918.
InParanoidiQ9Z214.
KOiK15010.
OrthoDBiEOG091G0CQ0.
PhylomeDBiQ9Z214.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR000697. WH1/EVH1_dom.
[Graphical view]
PfamiPF00568. WH1. 1 hit.
[Graphical view]
SMARTiSM00461. WH1. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50229. WH1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Z214-1) [UniParc]FASTAAdd to basket
Also known as: 1c, Vesl-1L

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
MGEQPIFSTR AHVFQIDPNT KKNWVPTSKH AVTVSYFYDS TRNVYRIISL
60 70 80 90 100
DGSKAIINST ITPNMTFTKT SQKFGQWADS RANTVYGLGF SSEHHLSKFA
110 120 130 140 150
EKFQEFKEAA RLAKEKSQEK MELTSTPSQE SAGGDLQSPL TPESINGTDD
160 170 180 190 200
ERTPDVTQNS EPRAEPAQNA LPFSHSAGDR TQGLSHASSA ISKHWEAELA
210 220 230 240 250
TLKGNNAKLT AALLESTANV KQWKQQLAAY QEEAERLHKR VTELECVSSQ
260 270 280 290 300
ANAVHSHKTE LSQTVQELEE TLKVKEEEIE RLKQEIDNAR ELQEQRDSLT
310 320 330 340 350
QKLQEVEIRN KDLEGQLSEL EQRLEKSQSE QDAFRSNLKT LLEILDGKIF
360
ELTELRDNLA KLLECS
Length:366
Mass (Da):41,305
Last modified:November 28, 2003 - v2
Checksum:iA6A21CB14207A384
GO
Isoform 2 (identifier: Q9Z214-2) [UniParc]FASTAAdd to basket
Also known as: 1b

The sequence of this isoform differs from the canonical sequence as follows:
     176-187: Missing.

Show »
Length:354
Mass (Da):40,124
Checksum:iC8F4579BFE3E69BF
GO
Isoform 3 (identifier: Q9Z214-3) [UniParc]FASTAAdd to basket
Also known as: 1a, Vesl

The sequence of this isoform differs from the canonical sequence as follows:
     176-186: SAGDRTQGLSH → RYTFNSAIMIK
     187-366: Missing.

Show »
Length:186
Mass (Da):20,872
Checksum:i9845DA6E2574BF83
GO

Sequence cautioni

The sequence AAC53113 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti268L → R in BAA32477 (PubMed:9727012).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009066176 – 187Missing in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_009067176 – 186SAGDRTQGLSH → RYTFNSAIMIK in isoform 3. 5 PublicationsAdd BLAST11
Alternative sequenceiVSP_009068187 – 366Missing in isoform 3. 5 PublicationsAdd BLAST180

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92079 mRNA. Translation: AAC53113.1. Different initiation.
AB003726 mRNA. Translation: BAA21671.1.
AF093267 mRNA. Translation: AAC71031.1.
AF093268 mRNA. Translation: AAC71032.1.
AB017140 mRNA. Translation: BAA34311.1.
AB007688 mRNA. Translation: BAA32477.1.
AJ276327 mRNA. Translation: CAB77249.1.
AJ276328 mRNA. Translation: CAB77250.1.
RefSeqiNP_113895.1. NM_031707.1. [Q9Z214-1]
XP_006231837.1. XM_006231775.3. [Q9Z214-2]
UniGeneiRn.37500.

Genome annotation databases

EnsembliENSRNOT00000073871; ENSRNOP00000066634; ENSRNOG00000047014. [Q9Z214-2]
GeneIDi29546.
KEGGirno:29546.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92079 mRNA. Translation: AAC53113.1. Different initiation.
AB003726 mRNA. Translation: BAA21671.1.
AF093267 mRNA. Translation: AAC71031.1.
AF093268 mRNA. Translation: AAC71032.1.
AB017140 mRNA. Translation: BAA34311.1.
AB007688 mRNA. Translation: BAA32477.1.
AJ276327 mRNA. Translation: CAB77249.1.
AJ276328 mRNA. Translation: CAB77250.1.
RefSeqiNP_113895.1. NM_031707.1. [Q9Z214-1]
XP_006231837.1. XM_006231775.3. [Q9Z214-2]
UniGeneiRn.37500.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DDVX-ray1.90A1-111[»]
1DDWX-ray1.70A1-120[»]
1I2HX-ray1.80A1-163[»]
3CVEX-ray1.75A/B/C/D302-366[»]
ProteinModelPortaliQ9Z214.
SMRiQ9Z214.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248180. 11 interactors.
IntActiQ9Z214. 9 interactors.
MINTiMINT-1891037.
STRINGi10116.ENSRNOP00000065989.

PTM databases

iPTMnetiQ9Z214.
PhosphoSitePlusiQ9Z214.

Proteomic databases

PaxDbiQ9Z214.
PRIDEiQ9Z214.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000073871; ENSRNOP00000066634; ENSRNOG00000047014. [Q9Z214-2]
GeneIDi29546.
KEGGirno:29546.

Organism-specific databases

CTDi9456.
RGDi628725. Homer1.

Phylogenomic databases

eggNOGiENOG410IGRQ. Eukaryota.
ENOG410XQWT. LUCA.
GeneTreeiENSGT00390000017850.
HOVERGENiHBG051918.
InParanoidiQ9Z214.
KOiK15010.
OrthoDBiEOG091G0CQ0.
PhylomeDBiQ9Z214.

Enzyme and pathway databases

ReactomeiR-RNO-6794361. Interactions of neurexins and neuroligins at synapses.

Miscellaneous databases

EvolutionaryTraceiQ9Z214.
PROiQ9Z214.

Gene expression databases

BgeeiENSRNOG00000047014.
ExpressionAtlasiQ9Z214. baseline and differential.
GenevisibleiQ9Z214. RN.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR000697. WH1/EVH1_dom.
[Graphical view]
PfamiPF00568. WH1. 1 hit.
[Graphical view]
SMARTiSM00461. WH1. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50229. WH1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHOME1_RAT
AccessioniPrimary (citable) accession number: Q9Z214
Secondary accession number(s): O08567
, O88800, Q9QUJ8, Q9QWN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: November 28, 2003
Last modified: November 2, 2016
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.