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Protein

Homer protein homolog 1

Gene

Homer1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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. Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (PubMed:19345194).2 Publications

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-RNO-6794361 Neurexins and neuroligins

Names & Taxonomyi

Protein namesi
Recommended name:
Homer protein homolog 1Curated
Alternative name(s):
PSD-Zip451 Publication
VASP/Ena-related gene up-regulated during seizure and LTP 1
Short name:
Vesl-1By similarity
Gene namesi
Name:Homer1Imported
Synonyms:Homer, Vesl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi628725 Homer1

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

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24W → A: Disrupts binding to both GRM1 and SHANK3. Does not form the high-order complex with SHANK1. 2 Publications1
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
Mutagenesisi344I → R: Dimeric form; when associated with E-349. Does not form the high-order complex with SHANK1; when associated with E-349. Does not change its interaction with STX12; when associated with E-349. Reduces localization to the spine; when associated with E-349. Affects dendritic spine structure; when associated with E-349. Decreases synaptic transmission; when associated with E-349. Does not affect glutamate receptors ratio; when associated with E-349. 1 Publication1
Mutagenesisi349I → E: Dimeric form; when associated with R-344. Does not form the high-order complex with SHANK1; when associated with R-344. Does not change its interaction with STX12; when associated with R-344. Reduces localization to the spine; when associated with R-344. Affects dendritic spine structure; when associated with R-344. Decreases synaptic transmission; when associated with R-344. Does not affect glutamate receptors ratio; when associated with R-344. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001910072 – 366Homer protein homolog 1Add BLAST365

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylglycineBy similarity1
Modified residuei318PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ9Z214
PRIDEiQ9Z214

PTM databases

iPTMnetiQ9Z214
PhosphoSitePlusiQ9Z214
SwissPalmiQ9Z214

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 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiQ9Z214 baseline and differential
GenevisibleiQ9Z214 RN

Interactioni

Subunit structurei

Tetramer; this tetrameric structure is critical for forming the high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (PubMed:19345194). Interacts with GRM1, GRM5, ITPR1, DYN3, RYR1, RYR2 and SHANK3 (PubMed:10433269, PubMed:10798399, PubMed:12810060, PubMed:12887973, PubMed:9069287, PubMed:9808458, PubMed:9808459, PubMed:9727012). Interacts with IFT57 and OPHN1 (PubMed:15034583). Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Interacts with SHANK1; forms high-order polymerized complex with a mesh-like network structure, at least composed of SHANK1, HOMER1 and DLGAP1; the complex formation is SHANK1 multimerization dependent (PubMed:10433269, PubMed:19345194).11 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248180, 11 interactors
ELMiQ9Z214
IntActiQ9Z214, 9 interactors
MINTiQ9Z214
STRINGi10116.ENSRNOP00000065989

Structurei

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Z214
SMRiQ9Z214
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z214

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni302 – 366Required for tetramerization1 PublicationAdd BLAST65

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. The coiled-Coil domain forms an antiparallel tetrameric arrangement (PubMed:19345194).1 Publication

Sequence similaritiesi

Belongs to the Homer family.Curated

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
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR000697 WH1/EVH1_dom
PfamiView protein in Pfam
PF00568 WH1, 1 hit
SMARTiView protein in SMART
SM00461 WH1, 1 hit
PROSITEiView protein in PROSITE
PS50229 WH1, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0H2UI35A0A0H2UI35_RAT
Homer protein homolog 1
Homer1
366Annotation score:
A0A0G2JYD5A0A0G2JYD5_RAT
Homer protein homolog 1
Homer1
190Annotation score:

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

Similar proteinsi

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
ELMiQ9Z214
IntActiQ9Z214, 9 interactors
MINTiQ9Z214
STRINGi10116.ENSRNOP00000065989

PTM databases

iPTMnetiQ9Z214
PhosphoSitePlusiQ9Z214
SwissPalmiQ9Z214

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 Neurexins and neuroligins

Miscellaneous databases

EvolutionaryTraceiQ9Z214
PROiPR:Q9Z214

Gene expression databases

BgeeiENSRNOG00000047014 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiQ9Z214 baseline and differential
GenevisibleiQ9Z214 RN

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR000697 WH1/EVH1_dom
PfamiView protein in Pfam
PF00568 WH1, 1 hit
SMARTiView protein in SMART
SM00461 WH1, 1 hit
PROSITEiView protein in PROSITE
PS50229 WH1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHOME1_RAT
AccessioniPrimary (citable) accession number: Q9Z214
Secondary accession number(s): O08567
, O88800, Q9QUJ8, Q9QWN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: November 28, 2003
Last modified: November 7, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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