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Protein

Homer protein homolog 3

Gene

HOMER3

Organism
Homo sapiens (Human)
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. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses. Negatively regulates T cell activation through negative regulation of IL2 expression by inhibiting calcineurin-NFAT pathway activation through interaction with NFATC2 leading to reduction of interaction between NFATC2 and PPP3CA (PubMed:18218901).1 Publication

GO - Molecular functioni

  • G protein-coupled glutamate receptor binding Source: GO_Central
  • identical protein binding Source: IntAct

GO - Biological processi

  • G protein-coupled glutamate receptor signaling pathway Source: GO_Central
  • negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
  • negative regulation of interleukin-2 production Source: UniProtKB
  • protein targeting Source: UniProtKB
  • regulation of store-operated calcium entry Source: GO_Central

Enzyme and pathway databases

ReactomeiR-HSA-6794361 Neurexins and neuroligins

Names & Taxonomyi

Protein namesi
Recommended name:
Homer protein homolog 3Curated
Short name:
Homer-3
Gene namesi
Name:HOMER3Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000051128.18
HGNCiHGNC:17514 HOMER3
MIMi604800 gene
neXtProtiNX_Q9NSC5

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, Cytoplasm, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22A → N: Does not affect interaction with NFATC2. Decreases interaction with NFATC2; when associated with 53-L--S-56. Decreases interaction with NFATC2; when associated with S-43 and 53-L--S-56. Markedly decreases interaction with NFATC2; when associated with T-30 and S-31 and 53-L--S-56. Impairs interaction with NFATC2; when associated with T-30; S-31; S-43 and 53-L--S-56. 1 Publication1
Mutagenesisi30 – 31AG → TS: Markedly decreases interaction with NFATC2; when associated with S-43 and 53-L--S-56. Markedly decreases interaction with NFATC2; when associated with N-22 and 53-L--S-56. Impairs interaction with NFATC2; when associated with N-22; S-43 and 53-L--S-56. 1 Publication2
Mutagenesisi36T → A: Does not affect interaction with NFATC2; when associated with A-38 and A-52. Attenuates inhibition by AKT; when associated with A-38 and A-52. 1 Publication1
Mutagenesisi38S → A: Does not affect interaction with NFATC2; when associated with A-36 and A-52. Attenuates inhibition by AKT; when associated with A-36 and A-52. 1 Publication1
Mutagenesisi43A → S: Does not affect interaction with NFATC2. Decreases interaction with NFATC2; when associated with N-22 and 53-L--S-56. Markedly decreases interaction with NFATC2; when associated with T-30; S-31 and 53-L--S-56. Impairs interaction with NFATC2; when associated with N-22; T-30; S-31 and 53-L--S-56. 1 Publication1
Mutagenesisi52S → A: Does not affect interaction with NFATC2; when associated with A-36 and A-38. Attenuates inhibition by AKT; when associated with A-36 and A-38. 1 Publication1
Mutagenesisi53 – 56IGGA → LDGS: Decreases interaction with NFATC2. Decreases interaction with NFATC2; when associated with N-22. Decreases interaction with NFATC2; when associated with N-22 and S-43. Markedly decreases interaction with NFATC2; when associated with T-30; S-31 and S-43. Markedly decreases interaction with NFATC2; when associated with N-22; T-30 and S-31. Impairs interaction with NFATC2; when associated with N-22; T-30, S-31 and S-43. 2 Publications4
Mutagenesisi54G → D: Decreases interaction with NFATC2. 1 Publication1

Organism-specific databases

DisGeNETi9454
OpenTargetsiENSG00000051128
PharmGKBiPA134988320

Polymorphism and mutation databases

BioMutaiHOMER3
DMDMi38605068

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001910111 – 361Homer protein homolog 3Add BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei120PhosphoserineBy similarity1
Modified residuei159PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NSC5
MaxQBiQ9NSC5
PaxDbiQ9NSC5
PeptideAtlasiQ9NSC5
PRIDEiQ9NSC5
ProteomicsDBi82529
82530 [Q9NSC5-2]
82531 [Q9NSC5-3]
82532 [Q9NSC5-4]

PTM databases

iPTMnetiQ9NSC5
PhosphoSitePlusiQ9NSC5

Expressioni

Gene expression databases

BgeeiENSG00000051128 Expressed in 218 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_HOMER3
ExpressionAtlasiQ9NSC5 baseline and differential
GenevisibleiQ9NSC5 HS

Organism-specific databases

HPAiCAB032656
CAB079015
HPA040999

Interactioni

Subunit structurei

Tetramer (PubMed:19345194). Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Interacts with NFATC2; interaction is calcium independent; interaction competes with PPP3CA for NFATC2 binding; interaction is reduced by AKT activation (PubMed:18218901). Interacts with NFATC1 and NFATC4 (PubMed:18218901). Interacts with SHANK1; forms a high-order complex at least composed of SHANK1 and HOMER3; the complex formation is regulated by CAMK2A-mediated phosphorylation (PubMed:19345194).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114843, 67 interactors
IntActiQ9NSC5, 104 interactors
MINTiQ9NSC5
STRINGi9606.ENSP00000376162

Structurei

Secondary structure

1361
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NSC5
SMRiQ9NSC5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NSC5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 113WH1PROSITE-ProRule annotationAdd BLAST113

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 80Required for interaction with NFATC21 PublicationAdd BLAST80

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili191 – 243Sequence analysisAdd BLAST53
Coiled coili254 – 358Sequence analysisAdd BLAST105

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi206 – 211Poly-Ala6

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IIX6 Eukaryota
ENOG41101PM LUCA
GeneTreeiENSGT00390000017850
HOGENOMiHOG000006979
HOVERGENiHBG051918
InParanoidiQ9NSC5
KOiK15010
OMAiQDKTELT
OrthoDBiEOG091G0CQ0
PhylomeDBiQ9NSC5
TreeFamiTF325627

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 (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NSC5-1) [UniParc]FASTAAdd to basket
Also known as: 3a

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
MSTAREQPIF STRAHVFQID PATKRNWIPA GKHALTVSYF YDATRNVYRI
60 70 80 90 100
ISIGGAKAII NSTVTPNMTF TKTSQKFGQW ADSRANTVYG LGFASEQHLT
110 120 130 140 150
QFAEKFQEVK EAARLAREKS QDGGELTSPA LGLASHQVPP SPLVSANGPG
160 170 180 190 200
EEKLFRSQSA DAPGPTERER LKKMLSEGSV GEVQWEAEFF ALQDSNNKLA
210 220 230 240 250
GALREANAAA AQWRQQLEAQ RAEAERLRQR VAELEAQAAS EVTPTGEKEG
260 270 280 290 300
LGQGQSLEQL EALVQTKDQE IQTLKSQTGG PREALEAAER EETQQKVQDL
310 320 330 340 350
ETRNAELEHQ LRAMERSLEE ARAERERARA EVGRAAQLLD VSLFELSELR
360
EGLARLAEAA P
Length:361
Mass (Da):39,836
Last modified:November 28, 2003 - v2
Checksum:i9FCC62319FF5165A
GO
Isoform 2 (identifier: Q9NSC5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     299-301: Missing.

Show »
Length:358
Mass (Da):39,479
Checksum:i0799594DEABE399F
GO
Isoform 3 (identifier: Q9NSC5-3) [UniParc]FASTAAdd to basket
Also known as: 3c

The sequence of this isoform differs from the canonical sequence as follows:
     124-145: GELTSPALGLASHQVPPSPLVS → WGGPQSALVVGSFGAVFELLIV
     146-361: Missing.

Show »
Length:145
Mass (Da):16,032
Checksum:i4DA4F12F2893744C
GO
Isoform 4 (identifier: Q9NSC5-4) [UniParc]FASTAAdd to basket
Also known as: 3d

The sequence of this isoform differs from the canonical sequence as follows:
     118-121: EKSQ → QLQR
     122-361: Missing.

Show »
Length:121
Mass (Da):13,685
Checksum:i42C572EB13211534
GO
Isoform 5 (identifier: Q9NSC5-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     101-136: Missing.

Show »
Length:325
Mass (Da):35,954
Checksum:iF51CA5A05CB92734
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R2U7M0R2U7_HUMAN
Homer protein homolog 3
HOMER3
243Annotation score:
M0QYF9M0QYF9_HUMAN
Homer protein homolog 3
HOMER3
152Annotation score:
M0QZN1M0QZN1_HUMAN
Homer protein homolog 3
HOMER3
150Annotation score:
M0R2T8M0R2T8_HUMAN
Homer protein homolog 3
HOMER3
85Annotation score:

Sequence cautioni

The sequence AAB81545 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017410342S → R4 PublicationsCorresponds to variant dbSNP:rs1059240Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045715101 – 136Missing in isoform 5. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_009073118 – 121EKSQ → QLQR in isoform 4. 1 Publication4
Alternative sequenceiVSP_009074122 – 361Missing in isoform 4. 1 PublicationAdd BLAST240
Alternative sequenceiVSP_009075124 – 145GELTS…SPLVS → WGGPQSALVVGSFGAVFELL IV in isoform 3. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_009076146 – 361Missing in isoform 3. 1 PublicationAdd BLAST216
Alternative sequenceiVSP_009077299 – 301Missing in isoform 2. 1 Publication3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF093265 mRNA Translation: AAC71029.1
Y17573 mRNA Translation: CAB75536.1
Y18894 mRNA Translation: CAB75543.1
Y18895 mRNA Translation: CAB75544.1
Y18896 mRNA Translation: CAB75545.1
AK124450 mRNA Translation: BAG54040.1
AK313995 mRNA Translation: BAG36707.1
AC002985 Genomic DNA Translation: AAB81545.1 Sequence problems.
CH471106 Genomic DNA Translation: EAW84763.1
BC012113 mRNA Translation: AAH12113.1
CCDSiCCDS12391.1 [Q9NSC5-1]
CCDS46022.1 [Q9NSC5-5]
CCDS46023.1 [Q9NSC5-2]
RefSeqiNP_001139193.1, NM_001145721.1 [Q9NSC5-2]
NP_001139194.1, NM_001145722.1 [Q9NSC5-1]
NP_001139196.1, NM_001145724.1 [Q9NSC5-5]
NP_004829.3, NM_004838.3 [Q9NSC5-1]
XP_006723006.1, XM_006722943.1 [Q9NSC5-1]
XP_006723007.1, XM_006722944.1 [Q9NSC5-1]
UniGeneiHs.720208

Genome annotation databases

EnsembliENST00000221222; ENSP00000221222; ENSG00000051128 [Q9NSC5-2]
ENST00000392351; ENSP00000376162; ENSG00000051128 [Q9NSC5-1]
ENST00000433218; ENSP00000396154; ENSG00000051128 [Q9NSC5-2]
ENST00000539827; ENSP00000439937; ENSG00000051128 [Q9NSC5-1]
ENST00000542541; ENSP00000446026; ENSG00000051128 [Q9NSC5-1]
ENST00000594439; ENSP00000471835; ENSG00000051128 [Q9NSC5-5]
GeneIDi9454
KEGGihsa:9454
UCSCiuc002nku.3 human [Q9NSC5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF093265 mRNA Translation: AAC71029.1
Y17573 mRNA Translation: CAB75536.1
Y18894 mRNA Translation: CAB75543.1
Y18895 mRNA Translation: CAB75544.1
Y18896 mRNA Translation: CAB75545.1
AK124450 mRNA Translation: BAG54040.1
AK313995 mRNA Translation: BAG36707.1
AC002985 Genomic DNA Translation: AAB81545.1 Sequence problems.
CH471106 Genomic DNA Translation: EAW84763.1
BC012113 mRNA Translation: AAH12113.1
CCDSiCCDS12391.1 [Q9NSC5-1]
CCDS46022.1 [Q9NSC5-5]
CCDS46023.1 [Q9NSC5-2]
RefSeqiNP_001139193.1, NM_001145721.1 [Q9NSC5-2]
NP_001139194.1, NM_001145722.1 [Q9NSC5-1]
NP_001139196.1, NM_001145724.1 [Q9NSC5-5]
NP_004829.3, NM_004838.3 [Q9NSC5-1]
XP_006723006.1, XM_006722943.1 [Q9NSC5-1]
XP_006723007.1, XM_006722944.1 [Q9NSC5-1]
UniGeneiHs.720208

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P8VX-ray1.85A2-118[»]
3CVFX-ray2.90A/B/C/D287-361[»]
ProteinModelPortaliQ9NSC5
SMRiQ9NSC5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114843, 67 interactors
IntActiQ9NSC5, 104 interactors
MINTiQ9NSC5
STRINGi9606.ENSP00000376162

PTM databases

iPTMnetiQ9NSC5
PhosphoSitePlusiQ9NSC5

Polymorphism and mutation databases

BioMutaiHOMER3
DMDMi38605068

Proteomic databases

EPDiQ9NSC5
MaxQBiQ9NSC5
PaxDbiQ9NSC5
PeptideAtlasiQ9NSC5
PRIDEiQ9NSC5
ProteomicsDBi82529
82530 [Q9NSC5-2]
82531 [Q9NSC5-3]
82532 [Q9NSC5-4]

Protocols and materials databases

DNASUi9454
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221222; ENSP00000221222; ENSG00000051128 [Q9NSC5-2]
ENST00000392351; ENSP00000376162; ENSG00000051128 [Q9NSC5-1]
ENST00000433218; ENSP00000396154; ENSG00000051128 [Q9NSC5-2]
ENST00000539827; ENSP00000439937; ENSG00000051128 [Q9NSC5-1]
ENST00000542541; ENSP00000446026; ENSG00000051128 [Q9NSC5-1]
ENST00000594439; ENSP00000471835; ENSG00000051128 [Q9NSC5-5]
GeneIDi9454
KEGGihsa:9454
UCSCiuc002nku.3 human [Q9NSC5-1]

Organism-specific databases

CTDi9454
DisGeNETi9454
EuPathDBiHostDB:ENSG00000051128.18
GeneCardsiHOMER3
HGNCiHGNC:17514 HOMER3
HPAiCAB032656
CAB079015
HPA040999
MIMi604800 gene
neXtProtiNX_Q9NSC5
OpenTargetsiENSG00000051128
PharmGKBiPA134988320
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIX6 Eukaryota
ENOG41101PM LUCA
GeneTreeiENSGT00390000017850
HOGENOMiHOG000006979
HOVERGENiHBG051918
InParanoidiQ9NSC5
KOiK15010
OMAiQDKTELT
OrthoDBiEOG091G0CQ0
PhylomeDBiQ9NSC5
TreeFamiTF325627

Enzyme and pathway databases

ReactomeiR-HSA-6794361 Neurexins and neuroligins

Miscellaneous databases

ChiTaRSiHOMER3 human
EvolutionaryTraceiQ9NSC5
GeneWikiiHOMER3
GenomeRNAii9454
PROiPR:Q9NSC5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000051128 Expressed in 218 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_HOMER3
ExpressionAtlasiQ9NSC5 baseline and differential
GenevisibleiQ9NSC5 HS

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 nameiHOME3_HUMAN
AccessioniPrimary (citable) accession number: Q9NSC5
Secondary accession number(s): B2RA10
, E9PCW9, O14580, O95350, Q9NSB9, Q9NSC0, Q9NSC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: November 28, 2003
Last modified: November 7, 2018
This is version 164 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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