Q9Z2Y3 (HOME1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homer protein homolog 1
Short name=Homer-1

Alternative name(s):
VASP/Ena-related gene up-regulated during seizure and LTP 1
Short name=Vesl-1

Gene names

Name:	Homer1
Synonyms:	Vesl1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	366 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Isoform 1 regulates the trafficking and surface expression of GRM5. 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 5 counteracts the effects by competing for binding sites. Isoform 3 regulates the trafficking and surface expression of GRM5. Isoform 5 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, isoform 2 and isoform 3 to regulate synaptic metabotropic glutamate function. Isoform 5, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development By similarity.
Subunit structure	Interacts with OPHN1 By similarity. Isoform 1, isoform 2 and isoform 3 encode a coiled-coil structure that mediates homo- and heteromultimerization. Interacts with IFT57. Ref.5 Ref.7 Ref.8
Subcellular location	Cytoplasm. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Cell junction › synapse. Note: Postsynaptic density of neuronal cells. Isoform 1 inhibits surface expression of GRM5 causing it to be retained in the endoplasmic reticulum. The N-terminal of isoform 2 may facilitate trafficking of the complex with GRM5 from the endoplasmic reticulum (ER) to the plasma membrane (PM).
Tissue specificity	Isoform 1, isoform 3 and isoform 5 are expressed in skeletal muscle at the level of the Z line, in heart, forebrain and cerebellum. Isoform 2, is a minor isoform and is expressed in cardiac and skeletal muscle. Isoform 5 is expressed in the postsynaptic region of neurons. Ref.7
Domain	The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3.
Sequence similarities	Belongs to the Homer family. Contains 1 WH1 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled glutamate receptor signaling pathway Traceable author statement Ref.1. Source: MGI behavioral response to cocaine Inferred from mutant phenotype PubMed 15294147. Source: MGI chemical homeostasis within a tissue Inferred from mutant phenotype PubMed 15294147. Source: MGI circadian rhythm Inferred from electronic annotation. Source: Compara positive regulation of calcium ion transport Inferred from mutant phenotype PubMed 18268005. Source: MGI protein localization to synapse Inferred from electronic annotation. Source: Compara regulation of calcium ion import Inferred from mutant phenotype PubMed 14505576. Source: BHF-UCL regulation of cation channel activity Inferred from mutant phenotype PubMed 14505576. Source: BHF-UCL regulation of store-operated calcium entry Inferred from mutant phenotype PubMed 14505576. Source: BHF-UCL response to calcium ion Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to stress Inferred from electronic annotation. Source: Compara skeletal muscle contraction Inferred from mutant phenotype PubMed 18268005. Source: MGI skeletal muscle fiber development Inferred from mutant phenotype PubMed 18268005. Source: MGI
Cellular_component	Z disc Inferred from direct assay PubMed 18268005. Source: MGI apical part of cell Inferred from direct assay PubMed 12860966. Source: MGI cell junction Inferred from electronic annotation. Source: UniProtKB-KW costamere Inferred from direct assay PubMed 18268005. Source: MGI dendritic shaft Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay Ref.2. Source: MGI postsynaptic density Inferred from direct assay PubMed 21558424PubMed 21664258. Source: BHF-UCL postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Z2Y3-1)

Also known as: 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.

Isoform 2 (identifier: Q9Z2Y3-2)

Also known as: 1d;

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MG → MLIHHHNRRALCKGSPTT
     176-187: Missing.

Isoform 3 (identifier: Q9Z2Y3-3)

Also known as: 1b;

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

Isoform 4 (identifier: Q9Z2Y3-4)

Also known as: Vesl-1M;

The sequence of this isoform differs from the canonical sequence as follows:
     177-203: AGDRTQALSHASSAISKHWEAELATLK → SSRWIFFPYCEDSQLSLLESSSGLGYF
     204-366: Missing.

Isoform 5 (identifier: Q9Z2Y3-5)

Also known as: Vesl-1S;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 366	366	Homer protein homolog 1		PRO_0000191006
Regions
	Domain	1 – 110	110	WH1
	Coiled coil	193 – 364	172	Potential
Natural variations
	Alternative sequence	1 – 2	2	MG → MLIHHHNRRALCKGSPTT in isoform 2.		VSP_009060
	Alternative sequence	176 – 187	12	Missing in isoform 2 and isoform 3.		VSP_009061
	Alternative sequence	176 – 186	11	SAGDRTQALSH → RYTFNSAIMIK in isoform 5.		VSP_009062
	Alternative sequence	177 – 203	27	AGDRT…LATLK → SSRWIFFPYCEDSQLSLLES SSGLGYF in isoform 4.		VSP_009063
	Alternative sequence	187 – 366	180	Missing in isoform 5.		VSP_009064
	Alternative sequence	204 – 366	163	Missing in isoform 4.		VSP_009065
Experimental info
	Sequence conflict	193	1	K → N in BAA34354. Ref.3
	Sequence conflict	197	1	A → V in BAA34354. Ref.3
	Sequence conflict	205	1	N → T in BAA34354. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Vesl-1L) [UniParc]. Last modified November 28, 2003. Version 2. Checksum: 6A4CBCE5B8A91A3F	FASTA	366	41,413
	10 20 30 40 50 60 MGEQPIFSTR AHVFQIDPNT KKNWVPTSKH AVTVSYFYDS TRNVYRIISL DGSKAIINST 70 80 90 100 110 120 ITPNMTFTKT SQKFGQWADS RANTVYGLGF SSEHHLSKFA EKFQEFKEAA RLAKEKSQEK 130 140 150 160 170 180 MELTSTPSQE SAGGDLQSPL TPESINGTDD ERTPDVTQNS EPRAEPTQNA LPFPHSAGDR 190 200 210 220 230 240 TQALSHASSA ISKHWEAELA TLKGNNAKLT AALLESTANV KQWKQQLAAY QEEAERLHKR 250 260 270 280 290 300 VTELECVSSQ ANAVHSHKTE LNQTVQELEE TLKVKEEEIE RLKQEIDNAR ELQEQRDSLT 310 320 330 340 350 360 QKLQEVEIRN KDLEGQLSDL EQRLEKSQNE QEAFRSNLKT LLEILDGKIF ELTELRDNLA KLLECS
	Isoform 2 (1d) [UniParc]. Checksum: ABBDD4A4184E2233	FASTA	370	42,084
	10 20 30 40 50 60 MLIHHHNRRA LCKGSPTTEQ PIFSTRAHVF QIDPNTKKNW VPTSKHAVTV SYFYDSTRNV 70 80 90 100 110 120 YRIISLDGSK AIINSTITPN MTFTKTSQKF GQWADSRANT VYGLGFSSEH HLSKFAEKFQ 130 140 150 160 170 180 EFKEAARLAK EKSQEKMELT STPSQESAGG DLQSPLTPES INGTDDERTP DVTQNSEPRA 190 200 210 220 230 240 EPTQNALPFP HSSAISKHWE AELATLKGNN AKLTAALLES TANVKQWKQQ LAAYQEEAER 250 260 270 280 290 300 LHKRVTELEC VSSQANAVHS HKTELNQTVQ ELEETLKVKE EEIERLKQEI DNARELQEQR 310 320 330 340 350 360 DSLTQKLQEV EIRNKDLEGQ LSDLEQRLEK SQNEQEAFRS NLKTLLEILD GKIFELTELR 370 DNLAKLLECS
	Isoform 3 (1b) [UniParc]. Checksum: F01D84B0A87E168C	FASTA	354	40,218
	10 20 30 40 50 60 MGEQPIFSTR AHVFQIDPNT KKNWVPTSKH AVTVSYFYDS TRNVYRIISL DGSKAIINST 70 80 90 100 110 120 ITPNMTFTKT SQKFGQWADS RANTVYGLGF SSEHHLSKFA EKFQEFKEAA RLAKEKSQEK 130 140 150 160 170 180 MELTSTPSQE SAGGDLQSPL TPESINGTDD ERTPDVTQNS EPRAEPTQNA LPFPHSSAIS 190 200 210 220 230 240 KHWEAELATL KGNNAKLTAA LLESTANVKQ WKQQLAAYQE EAERLHKRVT ELECVSSQAN 250 260 270 280 290 300 AVHSHKTELN QTVQELEETL KVKEEEIERL KQEIDNAREL QEQRDSLTQK LQEVEIRNKD 310 320 330 340 350 LEGQLSDLEQ RLEKSQNEQE AFRSNLKTLL EILDGKIFEL TELRDNLAKL LECS
	Isoform 4 (Vesl-1M) [UniParc]. Checksum: 19461F47996D04C3	FASTA	203	22,775
	10 20 30 40 50 60 MGEQPIFSTR AHVFQIDPNT KKNWVPTSKH AVTVSYFYDS TRNVYRIISL DGSKAIINST 70 80 90 100 110 120 ITPNMTFTKT SQKFGQWADS RANTVYGLGF SSEHHLSKFA EKFQEFKEAA RLAKEKSQEK 130 140 150 160 170 180 MELTSTPSQE SAGGDLQSPL TPESINGTDD ERTPDVTQNS EPRAEPTQNA LPFPHSSSRW 190 200 IFFPYCEDSQ LSLLESSSGL GYF
	Isoform 5 (Vesl-1S) [UniParc]. Checksum: 9845DA75270BBF83	FASTA	186	20,912
	10 20 30 40 50 60 MGEQPIFSTR AHVFQIDPNT KKNWVPTSKH AVTVSYFYDS TRNVYRIISL DGSKAIINST 70 80 90 100 110 120 ITPNMTFTKT SQKFGQWADS RANTVYGLGF SSEHHLSKFA EKFQEFKEAA RLAKEKSQEK 130 140 150 160 170 180 MELTSTPSQE SAGGDLQSPL TPESINGTDD ERTPDVTQNS EPRAEPTQNA LPFPHRYTFN SAIMIK

References

[1]	"Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins." Xiao B., Tu J.C., Petralia R.S., Yuan J.P., Doan A., Breder C.D., Ruggiero A., Lanahan A.A., Wenthold R.J., Worley P.F. Neuron 21:707-716(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5). Strain: C57BL/6J. Tissue: Forebrain.
[2]	"An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells." Saito H., Kimura M., Inanobe A., Ohe T., Kurachi Y. Biochem. Biophys. Res. Commun. 296:523-529(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: BALB/c. Tissue: Heart.
[3]	"Mouse Vesl family of EVH-protein that interacts with group I mGluRs." Inokuchi K., Hayashi F. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 5). Strain: C57BL/6N. Tissue: Brain cortex.
[4]	"Genomic structure of mouse vesl-1 gene." Hayashi F., Hirai K., Inokuchi K. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). Strain: 129/SvJ. Tissue: Hippocampus.
[5]	"Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors." Tu J.C., Xiao B., Yuan J.P., Lanahan A.A., Leoffert K., Li M., Linden D.J., Worley P.F. Neuron 21:717-726(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRM1; GRM5; DYN3 AND ITPR1.
[6]	"Homer: a link between neural activity and glutamate receptor function." Xiao B., Tu J.C., Worley P.F. Curr. Opin. Neurobiol. 10:370-374(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[7]	"Homer proteins and InsP(3) receptors co-localise in the longitudinal sarcoplasmic reticulum of skeletal muscle fibres." Salanova M., Priori G., Barone V., Intravaia E., Flucher B., Ciruela F., McIlhinney R.A.J., Parys J.B., Mikoshiba K., Sorrentino V. Cell Calcium 32:193-200(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH ITPR1.
[8]	"Homer1c interacts with Hippi and protects striatal neurons from apoptosis." Sakamoto K., Yoshida S., Ikegami K., Minakami R., Kato A., Udo H., Sugiyama H. Biochem. Biophys. Res. Commun. 352:1-5(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IFT57.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF093257 mRNA. Translation: AAC71021.1. AF093258 mRNA. Translation: AAC71022.1. AY137385 mRNA. Translation: AAM95461.1. AB019478 mRNA. Translation: BAA34353.1. AB019479 mRNA. Translation: BAA34354.1. AB089435 mRNA. Translation: BAC07257.1.
IPI	IPI00170191. IPI00172234. IPI00282945. IPI00323731. IPI00395134.
RefSeq	NP_036112.1. NM_011982.2. NP_671705.2. NM_147176.2. NP_687036.1. NM_152134.2.
UniGene	Mm.37533.
3D structure databases
ProteinModelPortal	Q9Z2Y3.
SMR	Q9Z2Y3. Positions 1-143, 302-364.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Z2Y3. 4 interactions.
MINT	MINT-3370083.
Protein family/group databases
TCDB	8.A.29.1.1. Homer1 family of excitation-contraction coupling proteins.
PTM databases
PhosphoSite	Q9Z2Y3.
Proteomic databases
PaxDb	Q9Z2Y3.
PRIDE	Q9Z2Y3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000060490; ENSMUSP00000050471; ENSMUSG00000007617. ENSMUST00000079086; ENSMUSP00000078093; ENSMUSG00000007617. ENSMUST00000080127; ENSMUSP00000079026; ENSMUSG00000007617. ENSMUST00000102752; ENSMUSP00000099813; ENSMUSG00000007617. ENSMUST00000109492; ENSMUSP00000105118; ENSMUSG00000007617.
GeneID	26556.
KEGG	mmu:26556.
UCSC	uc007rlc.2. mouse. uc007rld.2. mouse. uc007rle.2. mouse.
Organism-specific databases
CTD	9456.
MGI	MGI:1347345. Homer1.
Phylogenomic databases
eggNOG	NOG68331.
GeneTree	ENSGT00390000017850.
HOGENOM	HOG000006979.
HOVERGEN	HBG051918.
KO	K15010.
OMA	QNSEPRP.
Gene expression databases
ArrayExpress	Q9Z2Y3.
Bgee	Q9Z2Y3.
CleanEx	MM_HOMER1.
Genevestigator	Q9Z2Y3.
GermOnline	ENSMUSG00000007617. Mus musculus.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR000697. EVH1. IPR011993. PH_like_dom. [Graphical view]
Pfam	PF00568. WH1. 1 hit. [Graphical view]
SMART	SM00461. WH1. 1 hit. [Graphical view]
PROSITE	PS50229. WH1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	304603.
SOURCE	Search...

Entry information

Entry name

HOME1_MOUSE

Accession

Primary (citable) accession number: Q9Z2Y3
Secondary accession number(s): Q8K3E1 , Q8K4M8, Q9Z0E9, Q9Z216

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2003
Last sequence update:	November 28, 2003
Last modified:	April 3, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program