UniProtKB - Q9NSC5 (HOME3_HUMAN)
Homer protein homolog 3
HOMER3
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 by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (PubMed:18218901).
1 PublicationGO - 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
PathwayCommonsi | Q9NSC5 |
Reactomei | R-HSA-6794361, Neurexins and neuroligins |
SignaLinki | Q9NSC5 |
SIGNORi | Q9NSC5 |
Names & Taxonomyi
Protein namesi | Recommended name: Homer protein homolog 3CuratedShort name: Homer-3 |
Gene namesi | Name:HOMER3Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17514, HOMER3 |
MIMi | 604800, gene |
neXtProti | NX_Q9NSC5 |
VEuPathDBi | HostDB:ENSG00000051128 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Other locations
- postsynaptic density By similarity
- synapse By similarity
Note: Postsynaptic density of neuronal cells.By similarity
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
- dendrite Source: GO_Central
- postsynaptic density Source: GO_Central
Keywords - Cellular componenti
Cell junction, Cytoplasm, SynapsePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 22 | A → 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 Publication | 1 | |
Mutagenesisi | 30 – 31 | AG → 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 Publication | 2 | |
Mutagenesisi | 36 | T → 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 Publication | 1 | |
Mutagenesisi | 38 | S → 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 Publication | 1 | |
Mutagenesisi | 43 | A → 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 Publication | 1 | |
Mutagenesisi | 52 | S → 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 Publication | 1 | |
Mutagenesisi | 53 – 56 | IGGA → 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 Publications | 4 | |
Mutagenesisi | 54 | G → D: Decreases interaction with NFATC2. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9454 |
OpenTargetsi | ENSG00000051128 |
PharmGKBi | PA134988320 |
Miscellaneous databases
Pharosi | Q9NSC5, Tbio |
Genetic variation databases
BioMutai | HOMER3 |
DMDMi | 38605068 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000191011 | 1 – 361 | Homer protein homolog 3Add BLAST | 361 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 120 | PhosphoserineBy similarity | 1 | |
Modified residuei | 159 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9NSC5 |
jPOSTi | Q9NSC5 |
MassIVEi | Q9NSC5 |
MaxQBi | Q9NSC5 |
PaxDbi | Q9NSC5 |
PeptideAtlasi | Q9NSC5 |
PRIDEi | Q9NSC5 |
ProteomicsDBi | 19531 82529 [Q9NSC5-1] 82530 [Q9NSC5-2] 82531 [Q9NSC5-3] 82532 [Q9NSC5-4] |
PTM databases
iPTMneti | Q9NSC5 |
PhosphoSitePlusi | Q9NSC5 |
Expressioni
Gene expression databases
Bgeei | ENSG00000051128, Expressed in right hemisphere of cerebellum and 231 other tissues |
ExpressionAtlasi | Q9NSC5, baseline and differential |
Genevisiblei | Q9NSC5, HS |
Organism-specific databases
HPAi | ENSG00000051128, Tissue enhanced (lymphoid) |
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 PublicationsBinary interactionsi
Q9NSC5
GO - Molecular functioni
- G protein-coupled glutamate receptor binding Source: GO_Central
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 114843, 144 interactors |
CORUMi | Q9NSC5 |
IntActi | Q9NSC5, 128 interactors |
MINTi | Q9NSC5 |
STRINGi | 9606.ENSP00000439937 |
Miscellaneous databases
RNActi | Q9NSC5, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q9NSC5 |
BMRBi | Q9NSC5 |
SMRi | Q9NSC5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9NSC5 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 113 | WH1PROSITE-ProRule annotationAdd BLAST | 113 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 80 | Required for interaction with NFATC21 PublicationAdd BLAST | 80 | |
Regioni | 114 – 169 | DisorderedSequence analysisAdd BLAST | 56 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 191 – 243 | Sequence analysisAdd BLAST | 53 | |
Coiled coili | 254 – 358 | Sequence analysisAdd BLAST | 105 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | ENOG502R3T0, Eukaryota |
GeneTreei | ENSGT00940000158081 |
HOGENOMi | CLU_033940_0_0_1 |
InParanoidi | Q9NSC5 |
OMAi | KICDLKD |
OrthoDBi | 1251658at2759 |
PhylomeDBi | Q9NSC5 |
TreeFami | TF325627 |
Family and domain databases
CDDi | cd01206, EVH1_Homer_Vesl, 1 hit |
Gene3Di | 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR045027, Homer IPR044100, Homer_EVH1 IPR011993, PH-like_dom_sf IPR000697, WH1/EVH1_dom |
PANTHERi | PTHR10918, PTHR10918, 1 hit |
Pfami | View protein in Pfam PF00568, WH1, 1 hit |
SMARTi | View protein in SMART SM00461, WH1, 1 hit |
PROSITEi | View protein in PROSITE PS50229, WH1, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R2U7 | M0R2U7_HUMAN | Homer protein homolog 3 | HOMER3 | 243 | Annotation score: | ||
M0QZN1 | M0QZN1_HUMAN | Homer protein homolog 3 | HOMER3 | 150 | Annotation score: | ||
M0QYF9 | M0QYF9_HUMAN | Homer protein homolog 3 | HOMER3 | 152 | Annotation score: | ||
M0R2T8 | M0R2T8_HUMAN | Homer protein homolog 3 | HOMER3 | 85 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017410 | 342 | S → R4 PublicationsCorresponds to variant dbSNP:rs1059240Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045715 | 101 – 136 | Missing in isoform 5. 1 PublicationAdd BLAST | 36 | |
Alternative sequenceiVSP_009073 | 118 – 121 | EKSQ → QLQR in isoform 4. 1 Publication | 4 | |
Alternative sequenceiVSP_009074 | 122 – 361 | Missing in isoform 4. 1 PublicationAdd BLAST | 240 | |
Alternative sequenceiVSP_009075 | 124 – 145 | GELTS…SPLVS → WGGPQSALVVGSFGAVFELL IV in isoform 3. 1 PublicationAdd BLAST | 22 | |
Alternative sequenceiVSP_009076 | 146 – 361 | Missing in isoform 3. 1 PublicationAdd BLAST | 216 | |
Alternative sequenceiVSP_009077 | 299 – 301 | Missing in isoform 2. 1 Publication | 3 |
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 |
CCDSi | CCDS12391.1 [Q9NSC5-1] CCDS46022.1 [Q9NSC5-5] CCDS46023.1 [Q9NSC5-2] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000221222.15; ENSP00000221222.11; ENSG00000051128.19 [Q9NSC5-2] ENST00000392351.8; ENSP00000376162.2; ENSG00000051128.19 ENST00000433218.6; ENSP00000396154.2; ENSG00000051128.19 [Q9NSC5-2] ENST00000539827.5; ENSP00000439937.1; ENSG00000051128.19 ENST00000542541.6; ENSP00000446026.1; ENSG00000051128.19 ENST00000594439.5; ENSP00000471835.1; ENSG00000051128.19 [Q9NSC5-5] |
GeneIDi | 9454 |
KEGGi | hsa:9454 |
MANE-Selecti | ENST00000392351.8; ENSP00000376162.2; NM_004838.4; NP_004829.3 |
UCSCi | uc002nku.3, human [Q9NSC5-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS12391.1 [Q9NSC5-1] CCDS46022.1 [Q9NSC5-5] CCDS46023.1 [Q9NSC5-2] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2P8V | X-ray | 1.85 | A | 2-118 | [»] | |
3CVF | X-ray | 2.90 | A/B/C/D | 287-361 | [»] | |
AlphaFoldDBi | Q9NSC5 | |||||
BMRBi | Q9NSC5 | |||||
SMRi | Q9NSC5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114843, 144 interactors |
CORUMi | Q9NSC5 |
IntActi | Q9NSC5, 128 interactors |
MINTi | Q9NSC5 |
STRINGi | 9606.ENSP00000439937 |
PTM databases
iPTMneti | Q9NSC5 |
PhosphoSitePlusi | Q9NSC5 |
Genetic variation databases
BioMutai | HOMER3 |
DMDMi | 38605068 |
Proteomic databases
EPDi | Q9NSC5 |
jPOSTi | Q9NSC5 |
MassIVEi | Q9NSC5 |
MaxQBi | Q9NSC5 |
PaxDbi | Q9NSC5 |
PeptideAtlasi | Q9NSC5 |
PRIDEi | Q9NSC5 |
ProteomicsDBi | 19531 82529 [Q9NSC5-1] 82530 [Q9NSC5-2] 82531 [Q9NSC5-3] 82532 [Q9NSC5-4] |
Protocols and materials databases
Antibodypediai | 28304, 234 antibodies from 26 providers |
DNASUi | 9454 |
Genome annotation databases
Organism-specific databases
CTDi | 9454 |
DisGeNETi | 9454 |
GeneCardsi | HOMER3 |
HGNCi | HGNC:17514, HOMER3 |
HPAi | ENSG00000051128, Tissue enhanced (lymphoid) |
MIMi | 604800, gene |
neXtProti | NX_Q9NSC5 |
OpenTargetsi | ENSG00000051128 |
PharmGKBi | PA134988320 |
VEuPathDBi | HostDB:ENSG00000051128 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502R3T0, Eukaryota |
GeneTreei | ENSGT00940000158081 |
HOGENOMi | CLU_033940_0_0_1 |
InParanoidi | Q9NSC5 |
OMAi | KICDLKD |
OrthoDBi | 1251658at2759 |
PhylomeDBi | Q9NSC5 |
TreeFami | TF325627 |
Enzyme and pathway databases
PathwayCommonsi | Q9NSC5 |
Reactomei | R-HSA-6794361, Neurexins and neuroligins |
SignaLinki | Q9NSC5 |
SIGNORi | Q9NSC5 |
Miscellaneous databases
BioGRID-ORCSi | 9454, 39 hits in 1082 CRISPR screens |
EvolutionaryTracei | Q9NSC5 |
GeneWikii | HOMER3 |
GenomeRNAii | 9454 |
Pharosi | Q9NSC5, Tbio |
PROi | PR:Q9NSC5 |
RNActi | Q9NSC5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000051128, Expressed in right hemisphere of cerebellum and 231 other tissues |
ExpressionAtlasi | Q9NSC5, baseline and differential |
Genevisiblei | Q9NSC5, HS |
Family and domain databases
CDDi | cd01206, EVH1_Homer_Vesl, 1 hit |
Gene3Di | 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR045027, Homer IPR044100, Homer_EVH1 IPR011993, PH-like_dom_sf IPR000697, WH1/EVH1_dom |
PANTHERi | PTHR10918, PTHR10918, 1 hit |
Pfami | View protein in Pfam PF00568, WH1, 1 hit |
SMARTi | View protein in SMART SM00461, WH1, 1 hit |
PROSITEi | View protein in PROSITE PS50229, WH1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HOME3_HUMAN | |
Accessioni | Q9NSC5Primary (citable) accession number: Q9NSC5 Secondary accession number(s): B2RA10 Q9NSC1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 28, 2003 |
Last sequence update: | November 28, 2003 | |
Last modified: | May 25, 2022 | |
This is version 186 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families