P97879 (GRIP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate receptor-interacting protein 1
Short name=GRIP-1

Alternative name(s):
AMPA receptor-interacting protein GRIP1

Gene names

Name:

Grip1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

Protein attributes

Sequence length	1112 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons. Ref.1
Subunit structure	Interacts with EFNB1, EPHA7, EPHB2, EFNB3, KIF5A, KIF5C, KIF5B and the C-terminal tail of PRLHR. Forms a ternary complex with GRIA2 and CSPG4 By similarity. Can form homomultimers or heteromultimers with GRIP2. Interacts with GRIA2, GRIA3, GRIPAP1/GRASP1, PPFIA1, PPFIA4, FRAS1, PLCD4, PTPRF and liprins-alpha. Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIA2 and leads to AMPAR complex disassembly. Interacts with SLC30A9 By similarity. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10
Subcellular location	Cytoplasm. Endomembrane system; Peripheral membrane protein. Cell junction › synapse › postsynaptic cell membrane. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Endoplasmic reticulum membrane; Peripheral membrane protein Potential. Note: Membrane-associated with vesicles, peri-Golgi complexes and endoplasmic reticulum. Enriched in postsynaptic plasma membrane and postsynaptic densities. Ref.2 Ref.3
Tissue specificity	Expressed in brain, testis and retina. In brain highly expressed in the olfactory bulb, cortex and hyppocampus and lower level in thalamus, cerebellum and spinal cord. In brain it is found in the perikaryon, dendrites, dendritic shafts, dendritic spines and, excitatory and inhibitory synapses of neurons. In retina, it is most abundant in the plexiform layers than in perikarya. Ref.1 Ref.3 Ref.6
Developmental stage	Detected in early embryonic stage as early as E15, gradually increased throughout early development, peaked at approximately between postnatal days P6 and P8, then slightly decreased and remained relatively stable in the adult. Ref.3
Domain	PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1 and EPHB2 and with the C-terminus of PPFIA1 and PPFIA4. PDZ 4 and PDZ 5 mediate interaction with PRLHR By similarity. PDZ 4 and PDZ 5 mediate interaction with the C-terminus of GRIA2 and GRIA3. PDZ 4, PDZ 5 and PDZ 6 mediate homomultimers. PDZ 7 mediates interaction with PDZ domain of GRASP1. PDZ 7 domain binds CSPG4. PDZ 6 mediates interaction with the C-terminus of liprins-alpha. PDZ 1, PDZ 2 and PDZ 3 mediate interaction with the PDZ-binding motif of FRAS1. Ref.9
Sequence similarities	Contains 7 PDZ (DHR) domains.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Endoplasmic reticulum Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nervous system development Inferred from mutant phenotype Ref.5. Source: RGD protein transport Inferred from mutant phenotype PubMed 18160640. Source: RGD
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell neuronal cell body Inferred from direct assay PubMed 1041498. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Gria2	P19491	3	EBI-936113,EBI-77718
Grip2	Q9WTW1-3	3	EBI-936113,EBI-936068

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P97879-1)

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.

Note: No experimental confirmation available.

Isoform 2 (identifier: P97879-2)

Also known as: GRIP1c4-7;

The sequence of this isoform differs from the canonical sequence as follows:
     1-416: Missing.
     417-451: SSLNMGTLPRSLYSTSPRGTMMRRRLKKKDFKSSL → MTPKRTEKEMKKPHNFHHASHPPLRKGQKINAAHV
     1101-1112: GNLETREPTNTL → IPGDAVYFWQS

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1112

1112

Glutamate receptor-interacting protein 1

PRO_0000083851

Regions

Domain

53 – 136

84

PDZ 1

Domain

150 – 238

89

PDZ 2

Domain

252 – 336

85

PDZ 3

Domain

471 – 560

90

PDZ 4

Domain

572 – 657

86

PDZ 5

Domain

672 – 754

83

PDZ 6

Domain

988 – 1070

83

PDZ 7

Amino acid modifications

Modified residue

43

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 416

416

Missing in isoform 2.

VSP_009751

Alternative sequence

417 – 451

35

SSLNM…FKSSL → MTPKRTEKEMKKPHNFHHAS HPPLRKGQKINAAHV in isoform 2.

VSP_009752

Alternative sequence

1101 – 1112

12

GNLET…PTNTL → IPGDAVYFWQS in isoform 2.

VSP_009753

Experimental info

Sequence conflict

816

1

R → S in AAR08916. Ref.2

Sequence conflict

841

1

K → Q in AAR08916. Ref.2

Secondary structure

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1112

Helix Strand Turn

Details...

Beta strand

49 – 57

9

Beta strand

66 – 69

4

Beta strand

74 – 76

3

Beta strand

78 – 83

6

Helix

88 – 91

4

Beta strand

100 – 104

5

Helix

114 – 122

9

Beta strand

126 – 135

10

Beta strand

144 – 156

13

Beta strand

163 – 169

7

Turn

174 – 176

3

Beta strand

178 – 185

8

Helix

190 – 194

5

Beta strand

202 – 206

5

Helix

216 – 224

9

Beta strand

228 – 239

12

Beta strand

468 – 475

8

Turn

478 – 480

3

Beta strand

485 – 488

4

Beta strand

493 – 495

3

Beta strand

499 – 504

6

Helix

510 – 513

4

Beta strand

523 – 526

4

Helix

536 – 544

9

Beta strand

548 – 558

11

Beta strand

571 – 575

5

Beta strand

586 – 588

3

Beta strand

592 – 594

3

Beta strand

600 – 603

4

Beta strand

606 – 608

3

Helix

609 – 612

4

Beta strand

621 – 625

5

Helix

630 – 632

3

Helix

635 – 644

10

Beta strand

649 – 654

6

Beta strand

670 – 676

7

Beta strand

684 – 687

4

Beta strand

697 – 701

5

Helix

706 – 710

5

Beta strand

718 – 722

5

Helix

732 – 740

9

Beta strand

744 – 751

8

Beta strand

985 – 992

8

Beta strand

998 – 1006

9

Beta strand

1013 – 1018

6

Helix

1023 – 1027

5

Beta strand

1034 – 1038

5

Helix

1048 – 1056

9

Beta strand

1061 – 1068

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 2EFFFFE0D8609C59	FASTA	1,112	120,298
	10 20 30 40 50 60 MIAVSFKCRC QILRRLTKDE SPYTKSASQT KPPDGALAVR RQSIPEEFKG STVVELMKKE 70 80 90 100 110 120 GTTLGLTVSG GIDKDGKPRV SNLRQGGIAA RSDQLDVGDY IKAVNGINLA KFRHDEIISL 130 140 150 160 170 180 LKNVGERVVL EVEYELPPVS IQGSSVMFRT VEVTLHKEGN TFGFVIRGGA HDDRNKSRPV 190 200 210 220 230 240 VITCVRPGGP ADREGTIKPG DRLLSVDGIR LLGTTHAEAM SILKQCGQEA TLLIEYDVSV 250 260 270 280 290 300 MDSVATASGP LLVEVAKTPG ASLGVALTTS VCCNKQVIVI DKIKSASIAD RCGALHVGDH 310 320 330 340 350 360 ILSIDGTSME YCTLAEATQF LANTTDQVKL EILPHHQTRL ALKGPDHVKI QRSDRQLPWD 370 380 390 400 410 420 PWASSQCSVH TNHHHNPHHP DHCRVPALGF PKALTPNSPP AMVSSSSPTS MSAYSLSSLN 430 440 450 460 470 480 MGTLPRSLYS TSPRGTMMRR RLKKKDFKSS LSLASSTVGL AGQVVHTETT EVVLTADPVT 490 500 510 520 530 540 GFGIQLQGSV FATETLSSPP LISYIEADSP AERCGVLQIG DRVMAINGIP TEDSTFEEAN 550 560 570 580 590 600 QLLRDSSITS KVTLEIEFDV AESVIPSSGT FHVKLPKKHS VELGITISSP SSRKPGDPLV 610 620 630 640 650 660 ISDIKKGSVA HRTGTLELGD KLLAIDNIRL DSCSMEDAVQ ILQQCEDLVK LKIRKDEDNS 670 680 690 700 710 720 DEQESSGAII YTVELKRYGG PLGITISGTE EPFDPIIISS LTKGGLAERT GAIHIGDRIL 730 740 750 760 770 780 AINSSSLKGK PLSEAIHLLQ MAGETVTLKI KKQTDAQPAS SPKKLPIPSH SSDLGDGEED 790 800 810 820 830 840 PSPIQRPGKL SDVYPSTVPS VDSAVDSWDG SGIDARYGSQ GTTFQTSGYN FNTYDWRSPK 850 860 870 880 890 900 KRASLSPVPK PRSQTYPDVG LSNEDWDRST ASGFAGASDS ADAEQEENFW SQALEDLETC 910 920 930 940 950 960 GQSGILRELE ATIMSGSTMS LNHEAPTARS QLGRQASFQE RSNSRPHYSQ TTRSNTLPSD 970 980 990 1000 1010 1020 VGRKSVTLRK MKQEIKEIMS PTPVELHKVT LYKDSGMEDF GFSVADGLLE KGVYVKNIRP 1030 1040 1050 1060 1070 1080 AGPGDLGGLK PYDRLLQVNH VRTRDFDCCL VVPLIAESGN KLDLVISRNP LASQKSIEQP 1090 1100 1110 ALPSDWSEQN SAFFQQPSHG GNLETREPTN TL
	Isoform 2 (GRIP1c4-7) [UniParc]. Checksum: 0E8E0AE3EE7BCCDD	FASTA	695	75,383
	10 20 30 40 50 60 MTPKRTEKEM KKPHNFHHAS HPPLRKGQKI NAAHVSLASS TVGLAGQVVH TETTEVVLTA 70 80 90 100 110 120 DPVTGFGIQL QGSVFATETL SSPPLISYIE ADSPAERCGV LQIGDRVMAI NGIPTEDSTF 130 140 150 160 170 180 EEANQLLRDS SITSKVTLEI EFDVAESVIP SSGTFHVKLP KKHSVELGIT ISSPSSRKPG 190 200 210 220 230 240 DPLVISDIKK GSVAHRTGTL ELGDKLLAID NIRLDSCSME DAVQILQQCE DLVKLKIRKD 250 260 270 280 290 300 EDNSDEQESS GAIIYTVELK RYGGPLGITI SGTEEPFDPI IISSLTKGGL AERTGAIHIG 310 320 330 340 350 360 DRILAINSSS LKGKPLSEAI HLLQMAGETV TLKIKKQTDA QPASSPKKLP IPSHSSDLGD 370 380 390 400 410 420 GEEDPSPIQR PGKLSDVYPS TVPSVDSAVD SWDGSGIDAR YGSQGTTFQT SGYNFNTYDW 430 440 450 460 470 480 RSPKKRASLS PVPKPRSQTY PDVGLSNEDW DRSTASGFAG ASDSADAEQE ENFWSQALED 490 500 510 520 530 540 LETCGQSGIL RELEATIMSG STMSLNHEAP TARSQLGRQA SFQERSNSRP HYSQTTRSNT 550 560 570 580 590 600 LPSDVGRKSV TLRKMKQEIK EIMSPTPVEL HKVTLYKDSG MEDFGFSVAD GLLEKGVYVK 610 620 630 640 650 660 NIRPAGPGDL GGLKPYDRLL QVNHVRTRDF DCCLVVPLIA ESGNKLDLVI SRNPLASQKS 670 680 690 IEQPALPSDW SEQNSAFFQQ PSHGIPGDAV YFWQS

References

[1]	"GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors." Dong H., O'Brien R.J., Fung E.T., Lanahan A.A., Worley P.F., Huganir R.L. Nature 386:279-284(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH GRIA2 AND GRIA3, TISSUE SPECIFICITY, FUNCTION. Tissue: Hippocampus.
[2]	"A four PDZ domain-containing splice variant form of GRIP1 is localized in GABAergic and glutamatergic synapses in the brain." Charych E.I., Yu W., Li R., Serwanski D.R., Miralles C.P., Li X., Yang B.Y., Pinal N., Walikonis R., De Blas A.L. J. Biol. Chem. 279:38978-38990(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, INTERACTION WITH GRIA2 AND GRIA3. Strain: Sprague-Dawley. Tissue: Brain.
[3]	"Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2." Dong H., Zhang P., Song I., Petralia R.S., Liao D., Huganir R.L. J. Neurosci. 19:6930-6941(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, INTERACTION WITH GRIA2, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
[4]	"GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP complex." Ye B., Liao D., Zhang X., Zhang P., Dong H., Huganir R.L. Neuron 26:603-617(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRIPAP1.
[5]	"Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting." Wyszynski M., Kim E., Dunah A.W., Passafaro M., Valtschanoff J.G., Serra-Pages C., Streuli M., Weinberg R.J., Sheng M. Neuron 34:39-52(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPFIA1; PPFIA4; PTPRF AND LIPRINS-ALPHA.
[6]	"Association of the AMPA receptor-related postsynaptic density proteins GRIP and ABP with subsets of glutamate-sensitive neurons in the rat retina." Gabriel R., de Souza S., Ziff E.B., Witkovsky P. J. Comp. Neurol. 449:129-140(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior." Zhang J., Wang Y., Chi Z., Keuss M.J., Pai Y.M., Kang H.C., Shin J.H., Bugayenko A., Wang H., Xiong Y., Pletnikov M.V., Mattson M.P., Dawson T.M., Dawson V.L. Cell 145:284-299(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATAD1 AND GRIA2.
[8]	"PDZ7 of glutamate receptor interacting protein binds to its target via a novel hydrophobic surface area." Feng W., Fan J.-S., Jiang M., Shi Y.-W., Zhang M. J. Biol. Chem. 277:41140-41146(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 980-1070, INTERACTION WITH GRASP1.
[9]	"The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. Implications for glial-neuronal signaling." Stegmueller J., Werner H., Nave K.-A., Trotter J. J. Biol. Chem. 278:3590-3598(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSPG4, DOMAIN.
[10]	"A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1." Takamiya K., Kostourou V., Adams S., Jadeja S., Chalepakis G., Scambler P.J., Huganir R.L., Adams R.H. Nat. Genet. 36:172-177(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FRAS1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U88572 mRNA. Translation: AAB51689.1.
AY437398 mRNA. Translation: AAR08916.1.

IPI

IPI00208830.
IPI00948929.

PIR

T32733.

RefSeq

NP_114458.1. NM_032069.1.

UniGene

Rn.74240.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M5Z	NMR	-	A	980-1070	[»]
1N7E	X-ray	1.50	A	665-761	[»]
1N7F	X-ray	1.80	A/B	665-761	[»]
1P1D	NMR	-	A	463-658	[»]
1P1E	NMR	-	A	463-563	[»]
2QT5	X-ray	2.30	A/B	48-243	[»]

ProteinModelPortal

P97879.

SMR

P97879. Positions 48-240, 242-343, 463-658, 667-761, 980-1070.

ModBase

Search...

Protein-protein interaction databases

IntAct

P97879. 6 interactions.

MINT

MINT-138947.

STRING

10116.ENSRNOP00000061369.

PTM databases

PhosphoSite

P97879.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000005545; ENSRNOP00000005545; ENSRNOG00000004013.

GeneID

84016.

KEGG

rno:84016.

Organism-specific databases

CTD

23426.

RGD

621667. Grip1.

Phylogenomic databases

eggNOG

NOG297474.

GeneTree

ENSGT00390000013494.

HOGENOM

HOG000043120.

HOVERGEN

HBG051841.

InParanoid

P97879.

Gene expression databases

ArrayExpress

P97879.

Genevestigator

P97879.

GermOnline

ENSRNOG00000004013. Rattus norvegicus.

Family and domain databases

InterPro

IPR001478. PDZ.
[Graphical view]

Pfam

PF00595. PDZ. 7 hits.
[Graphical view]

SMART

SM00228. PDZ. 7 hits.
[Graphical view]

SUPFAM

SSF50156. PDZ. 7 hits.

PROSITE

PS50106. PDZ. 7 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P97879.

NextBio

616561.

Entry information

Entry name

GRIP1_RAT

Accession

Primary (citable) accession number: P97879

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	May 1, 1997
Last modified:	April 3, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program