Q9Z214 (HOME1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Homer1
Synonyms:	Homer, Vesl

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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. 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. Ref.12
Subunit structure	Interacts with IFT57 By similarity. Interacts with OPHN1. Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Ref.1 Ref.3 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
Subcellular location	Cytoplasm By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Cell junction › synapse By similarity. Note: Postsynaptic density of neuronal cells. Isoform 1 inhibits surface expression of GRM5 causing it to be retained in the endoplasmic reticulum By similarity. Ref.8
Tissue specificity	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. Ref.6
Developmental stage	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.
Induction	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.
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.
Sequence caution	The sequence AAC53113.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein coupled glutamate receptor signaling pathway Inferred from direct assay Ref.1. Source: RGD circadian rhythm Inferred from expression pattern. Source: RGD protein localization to synapse Inferred from direct assay. Source: BHF-UCL response to cocaine Inferred from expression pattern. Source: RGD response to nicotine Inferred from expression pattern. Source: RGD response to stress Inferred from expression pattern. Source: RGD
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell dendritic shaft Inferred from direct assay Ref.1. Source: RGD neuronal cell body Inferred from direct assay Ref.1. Source: RGD plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic density Inferred from direct assay Ref.8. Source: BHF-UCL postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW synaptosome Inferred from direct assay. Source: RGD
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct protein binding Inferred from physical interaction Ref.12. Source: IntAct protein complex scaffold Inferred from physical interaction Ref.8. Source: BHF-UCL protein heterodimerization activity Inferred from physical interaction Ref.5. Source: RGD scaffold protein binding Inferred from physical interaction Ref.8. Source: BHF-UCL type 5 metabotropic glutamate receptor binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Agap2	Q8CGU4	4	EBI-4410552,EBI-4409108
Shank1	Q9WV48	4	EBI-2338999,EBI-80909

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Z214-1)

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.

Isoform 2 (identifier: Q9Z214-2)

Also known as: 1b;

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

Isoform 3 (identifier: Q9Z214-3)

Also known as: 1a; Vesl;

The sequence of this isoform differs from the canonical sequence as follows:
     176-186: SAGDRTQGLSH → 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_0000191007

Regions

Domain

1 – 110

110

WH1

Coiled coil

193 – 364

172

Potential

Natural variations

Alternative sequence

176 – 187

12

Missing in isoform 2.

VSP_009066

Alternative sequence

176 – 186

11

SAGDRTQGLSH → RYTFNSAIMIK in isoform 3.

VSP_009067

Alternative sequence

187 – 366

180

Missing in isoform 3.

VSP_009068

Experimental info

Mutagenesis

24

1

W → A: Disrupts binding to both GRM1 and SHANK3. Ref.14

Mutagenesis

24

1

W → Y: Disrupts binding to GRM1. Ref.14

Mutagenesis

70

1

T → A: Normal binding. Ref.14

Mutagenesis

70

1

T → E: Disrupts binding to SHANK3. Ref.14

Mutagenesis

74

1

F → A: Eliminates binding to both GRM1 and SHANK3. Ref.14

Mutagenesis

76

1

Q → A: Normal binding. Ref.14

Mutagenesis

76

1

Q → R: Normal binding. Ref.14

Mutagenesis

85

1

V → A: Diminishes binding to GRM1. Ref.14

Mutagenesis

89

1

G → A: Eliminates binding to both GRM1 and SHANK3. Ref.14

Mutagenesis

89

1

G → N: Eliminates binding to both GRM1 and SHANK3. Ref.14

Sequence conflict

268

1

L → R in BAA32477. Ref.5

Secondary structure

1

.

.

.

.

.

.

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.

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.

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.

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366

Helix Strand Turn

Details...

Beta strand

3 – 5

3

Beta strand

7 – 16

10

Turn

18 – 20

3

Beta strand

23 – 30

8

Beta strand

32 – 38

7

Turn

40 – 42

3

Beta strand

45 – 51

7

Beta strand

54 – 60

7

Beta strand

71 – 79

9

Turn

80 – 83

4

Beta strand

84 – 89

6

Helix

93 – 107

15

Helix

112 – 116

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (1c) (Vesl-1L) [UniParc]. Last modified November 28, 2003. Version 2. Checksum: A6A21CB14207A384	FASTA	366	41,305
	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 EPRAEPAQNA LPFSHSAGDR 190 200 210 220 230 240 TQGLSHASSA ISKHWEAELA TLKGNNAKLT AALLESTANV KQWKQQLAAY QEEAERLHKR 250 260 270 280 290 300 VTELECVSSQ ANAVHSHKTE LSQTVQELEE TLKVKEEEIE RLKQEIDNAR ELQEQRDSLT 310 320 330 340 350 360 QKLQEVEIRN KDLEGQLSEL EQRLEKSQSE QDAFRSNLKT LLEILDGKIF ELTELRDNLA KLLECS
	Isoform 2 (1b) [UniParc]. Checksum: C8F4579BFE3E69BF	FASTA	354	40,124
	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 EPRAEPAQNA LPFSHSSAIS 190 200 210 220 230 240 KHWEAELATL KGNNAKLTAA LLESTANVKQ WKQQLAAYQE EAERLHKRVT ELECVSSQAN 250 260 270 280 290 300 AVHSHKTELS QTVQELEETL KVKEEEIERL KQEIDNAREL QEQRDSLTQK LQEVEIRNKD 310 320 330 340 350 LEGQLSELEQ RLEKSQSEQD AFRSNLKTLL EILDGKIFEL TELRDNLAKL LECS
	Isoform 3 (1a) (Vesl) [UniParc]. Checksum: 9845DA6E2574BF83	FASTA	186	20,872
	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 EPRAEPAQNA LPFSHRYTFN SAIMIK

References

[1]	"Homer: a protein that selectively binds metabotropic glutamate receptors." Brakeman P.R., Lanahan A.A., O'Brien R., Roche K., Barnes C.A., Huganir R.L., Worley P.F. Nature 386:284-288(1997) [PubMed: 9069287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH GRM1 AND GRM5. Strain: Sprague-Dawley. Tissue: Hippocampus.
[2]	"Vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis." Kato A., Ozawa F., Saitoh Y., Hirai K., Inokuchi K. FEBS Lett. 412:183-189(1997) [PubMed: 9257717] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), CHARACTERIZATION. Strain: Wistar. Tissue: Hippocampus.
[3]	"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: 9808458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), CHARACTERIZATION, INTERACTION WITH GRM1 AND GRM5. Strain: Sprague-Dawley. Tissue: Hippocampus.
[4]	"Isolation of PSD-Zip45, a novel Homer/vesl family protein containing leucine zipper motifs, from rat brain." Sun J., Tadokoro S., Imanaka T., Murakami S.D., Nakamura M., Kashiwada K., Ko J., Nishida W., Sobue K. FEBS Lett. 437:304-308(1998) [PubMed: 9824313] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]	"Novel members of the Vesl/Homer family of PDZ-proteins that bind metabotropic glutamate receptors." Kato A., Ozawa F., Saitoh Y., Fukazawa Y., Sugiyama H., Inokuchi K. J. Biol. Chem. 273:23969-23975(1998) [PubMed: 9727012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH GRM1 AND GRM5. Strain: Sprague-Dawley. Tissue: Hippocampus.
[6]	"Evidence for the presence of two homer 1 transcripts in skeletal and cardiac muscles." Sandona D., Tibaldo E., Volpe P. Biochem. Biophys. Res. Commun. 279:348-353(2000) [PubMed: 11118290] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY. Tissue: Fast-twitch skeletal muscle.
[7]	"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: 9808459] [Abstract] Cited for: INTERACTION WITH GRM1; GRM5; DYN3 AND ITPR1.
[8]	"Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins." Tu J.C., Xiao B., Naisbitt S., Yuan J.P., Petralia R.S., Brakeman P., Doan A., Aakalu V.K., Lanahan A.A., Sheng M., Worley P.F. Neuron 23:583-592(1999) [PubMed: 10433269] [Abstract] Cited for: INTERACTION WITH SHANK1 AND SHANK3, SUBCELLULAR LOCATION.
[9]	"Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling." Westhoff J.H., Hwang S.-Y., Scott Duncan R., Ozawa F., Volpe P., Inokuchi K., Koulen P. Cell Calcium 34:261-269(2003) [PubMed: 12887973] [Abstract] Cited for: INTERACTION WITH RYR2.
[10]	"Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling." Hwang S.-Y., Wei J., Westhoff J.H., Duncan R.S., Ozawa F., Volpe P., Inokuchi K., Koulen P. Cell Calcium 34:177-184(2003) [PubMed: 12810060] [Abstract] Cited for: INTERACTION WITH RYR1.
[11]	"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: 10851183] [Abstract] Cited for: REVIEW.
[12]	"PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis." Rong R., Ahn J.-Y., Huang H., Nagata E., Kalman D., Kapp J.A., Tu J., Worley P.F., Snyder S.H., Ye K. Nat. Neurosci. 6:1153-1161(2003) [PubMed: 14528310] [Abstract] Cited for: INTERACTION WITH AGAP2, FUNCTION.
[13]	"The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis." Govek E.E., Newey S.E., Akerman C.J., Cross J.R., Van der Veken L., Van Aelst L. Nat. Neurosci. 7:364-372(2004) [PubMed: 15034583] [Abstract] Cited for: INTERACTION WITH OPHN1.
[14]	"Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition." Beneken J., Tu J.C., Xiao B., Nuriya M., Yuan J.P., Worley P.F., Leahy D.J. Neuron 26:143-154(2000) [PubMed: 10798399] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-111 IN COMPLEX WITH GRM5, MUTAGENESIS OF TRP-24; THR-70; PHE-74; GLN-76; VAL-85 AND GLY-89.
[15]	"Crystal structure of the Homer 1 family conserved region reveals the interaction between the EVH1 domain and own proline-rich motif." Irie K., Nakatsu T., Mitsuoka K., Miyazawa A., Sobue K., Hiroaki Y., Doi T., Fujiyoshi Y., Kato H. J. Mol. Biol. 318:1117-1126(2002) [PubMed: 12054806] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-163.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00210570.
IPI00395307.
IPI00395308.

RefSeq

NP_113895.1. NM_031707.1.

UniGene

Rn.37500.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DDV	X-ray	1.90	A	1-111	[»]
1DDW	X-ray	1.70	A	1-120	[»]
1I2H	X-ray	1.80	A	1-163	[»]
3CVE	X-ray	1.75	A/B/C/D	302-366	[»]

ProteinModelPortal

Q9Z214.

SMR

Q9Z214. Positions 1-143.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Z214. 8 interactions.

STRING

Q9Z214.

Proteomic databases

PRIDE

Q9Z214.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

29546.

KEGG

rno:29546.

Organism-specific databases

CTD

9456.

RGD

628725. Homer1.

Phylogenomic databases

HOVERGEN

HBG051918.

Gene expression databases

Genevestigator

Q9Z214.

Family and domain databases

InterPro

IPR000697. EVH1.
IPR010356. Haemolysin_E.
IPR011993. PH_type.
[Graphical view]

Gene3D

G3DSA:1.20.1170.10. Haemolysin_E. 1 hit.
G3DSA:2.30.29.30. PH_type. 1 hit.

KO

K15010.

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

609561.

Entry information

Entry name

HOME1_RAT

Accession

Primary (citable) accession number: Q9Z214
Secondary accession number(s): O08567 , O88800, Q9QUJ8, Q9QWN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2003
Last sequence update:	November 28, 2003
Last modified:	January 25, 2012
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program