Reviewed, UniProtKB/Swiss-Prot Q9WTW1 (GRIP2_RAT)

Names and origin

Protein names

Recommended name:
    Glutamate receptor-interacting protein 2
      Short name=GRIP2 protein
Alternative name(s):
    AMPA receptor-interacting protein GRIP2

Gene names

Name:

Grip2

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	1043 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subunit structure	Interacts with the C-terminal tail of PRLHR By similarity. Interacts with EFNB1, EFNB3, GRIA2, GRIA3, CSGP4 and GRIPAP1. Can form homomultimers and heteromultimers with GRIP1.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Cell junction › synapse. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Note: Isoform 1 and isoform 3 were found in synaptic plasma membrane and postsynaptic density. Isoform 3 was also found in dendrites where it was associated with microtubules, endoplasmic reticulum and dendritic spines. Isoform 2 was found at excitatory synapses and also at non-synaptic membranes and within intracellular compartments. Isoform 4 was exclusively membrane associated. Ref.1 Ref.3 Ref.4 Ref.5
Tissue specificity	Brain specific. Isoform 1 is expressed in the olfactory bulb, cortex and hippocampus and was also expressed at lower levels in thalamus, cerebellum and spinal cord. Isoform 3 is expressed in pyramidal cells of cortex and hippocampus, striatum, thalamus, hypothalamus, stellate cells of cerebellum, and brainstem. Isoform 2 and isoform 4 are expressed in cortex, hippocampus, thalamus, cerebellum, brainstem and spinal cord. In hippocampal neurons isoform 4 is found abundantly in spine structures. Isoform 2 is abundant in the cell body and also found in dendritic shafts. Ref.1 Ref.3 Ref.5
Developmental stage	Isoform 1 expression was relatively low early in development and increased postnatally, reaching a peak at P14. Isoform 3 is detected at low levels prior to P9, whereupon its expression increases, with the highest levels in the adult. Ref.1 Ref.3 Ref.2
Domain	PDZ 5 mediates the C-terminal binding of GRIA2 and GRIA3. PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1. PDZ 7 mediates interaction with CSPG4. Ref.7
Post-translational modification	Palmitoylation of isoform 4 mediates membrane location.
Sequence similarities	Belongs to the GRIP2 family. Contains 7 PDZ (DHR) domains.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Repeat
PTM	Lipoprotein Palmitate
Gene Ontology (GO)
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell dendrite Ref.1 Inferred from direct assay. Source: UniProtKB membrane fraction Ref.3 Inferred from direct assay. Source: RGD postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	identical protein binding Ref.1 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-936068,EBI-936068
Gria2	P19491	4	EBI-936068,EBI-77718
Grip1	P97879	1	EBI-936068,EBI-936113

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9WTW1-1)

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.

Isoform 2 (identifier: Q9WTW1-2)

Also known as: ABP-L; ABP-L/GRIP2;

The sequence of this isoform differs from the canonical sequence as follows:
     349-390: VRIQRSEQLHHWDPCVPSCHSPRPSHCRAPTWAPGGQDQSRS → A

Isoform 3 (identifier: Q9WTW1-3)

Also known as: ABP; ABP-S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.
     859-874: SPAPGPAREEGFWRVL → RHPVSPLSTPSHLPLF
     875-1043: Missing.

Isoform 4 (identifier: Q9WTW1-4)

Also known as: pABP-L;

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MLAVSLKWRLGVVRRRPK → MRGWRRNLALCLQRLPDE

Note: Palmitoylated on Cys-11.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1043	1043	Glutamate receptor-interacting protein 2		PRO_0000083853
Regions
	Domain	53 – 136	84	PDZ 1
	Domain	153 – 239	87	PDZ 2
	Domain	253 – 337	85	PDZ 3
	Domain	458 – 547	90	PDZ 4
	Domain	559 – 643	85	PDZ 5
	Domain	658 – 740	83	PDZ 6
	Domain	942 – 1024	83	PDZ 7
Natural variations
	Alternative sequence	1 – 52	52	Missing in isoform 3.		VSP_009760
	Alternative sequence	1 – 18	18	MLAVS…RRRPK → MRGWRRNLALCLQRLPDE in isoform 4.		VSP_009759
	Alternative sequence	349 – 390	42	VRIQR…DQSRS → A in isoform 2.		VSP_009761
	Alternative sequence	859 – 874	16	SPAPG…FWRVL → RHPVSPLSTPSHLPLF in isoform 3.		VSP_009762
	Alternative sequence	875 – 1043	169	Missing in isoform 3.		VSP_009763
Experimental info
	Sequence conflict	450	1	Q → H in AAD28427. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: C463C36ADC459A3C	FASTA	1,043	112,488
	10 20 30 40 50 60 MLAVSLKWRL GVVRRRPKDD GPYSKGGKDT AGTDGALVCR RQSIPEEFRG ITMVELIKRE 70 80 90 100 110 120 GSTLGLTISG GTDKDGKPRV SNLRPGGLAA RSDLLNVGDY IRSVNGIRLT RLRHDEIITL 130 140 150 160 170 180 LKNVGERVVL EVEYELPPPA PENNPRIISK TVDVSLYKEG NSFGFVLRGG AHEDLHKSRP 190 200 210 220 230 240 LVLTYVRPGG PADREGSLKV GDRLLSIDGI PLHGASHATA IATLQQCSHE ALFQVEYDVA 250 260 270 280 290 300 TPDTVANASG PLVVEIAKTP GSALGISLTT GSHRNKPAIT IDRIKPASVV DRSGALHAGD 310 320 330 340 350 360 HILAIDGTST EHCSLVEATK LLASVTEKVR LEILPAPQSR RPLKPPEAVR IQRSEQLHHW 370 380 390 400 410 420 DPCVPSCHSP RPSHCRAPTW APGGQDQSRS VSSTPFSSPT MNPAFPCANA STLPRGPMSP 430 440 450 460 470 480 RTTAGRRRQR RKEHRSSLSL ASSTVGPGGQ IVHTETTEVV LCGDPLSGFG LQLQGGIFAT 490 500 510 520 530 540 ETLSSPPLVR FIEPDSPAER CGLLQVGDRV LAINGIATED GTMEEANQLL RDAALARKVV 550 560 570 580 590 600 LEIEFDVAES VIPSSGTFHV KLPKRRGVEL GITISSASRK RGEPLIISDI KKGSVAHRTG 610 620 630 640 650 660 TLEPGDKLLA IDNIRLDHCP MEYAVQILRQ CEDLVKLKIR KDEDNSDEQE SSGAVSYTVE 670 680 690 700 710 720 LKRYGGPLGI TISGTEEPFD PIIISGLTKR GLAERTGAIH VGDRILAINS VSLKGRPLSE 730 740 750 760 770 780 AIHLLQVAGE TVTLKIKKQL DRPLLPRQSG SLSEASDVDE DPPEALKGGL LTTHFSPAVP 790 800 810 820 830 840 SVDSAVESWG SSATEGGFGG SGSYTPQVAV RSVTPQEWRS SRLKSSPPPL EPRRTSYTPG 850 860 870 880 890 900 PTDESFPEEE EGDWEPPMSP APGPAREEGF WRVLGEALED LESCGQSELL RELEASIMTG 910 920 930 940 950 960 TVQSVAVDGR PGSRPWRRSR EVGTSPEDLQ ELLLPTPLEM HRVTLHKDPV RNDFGFSVSD 970 980 990 1000 1010 1020 GLLEKGVYVH TVRIDGPAQH GGLQPFDRLL QVNHVRTRDF DCCLAVPLLA EAGDILELVV 1030 1040 SRNPLAQSRR TPGAPGPSSP QMI
	Isoform 2 (ABP-L) (ABP-L/GRIP2). Checksum: 117EB6D94D2091B0	FASTA	1,002	107,789
	10 20 30 40 50 60 MLAVSLKWRL GVVRRRPKDD GPYSKGGKDT AGTDGALVCR RQSIPEEFRG ITMVELIKRE 70 80 90 100 110 120 GSTLGLTISG GTDKDGKPRV SNLRPGGLAA RSDLLNVGDY IRSVNGIRLT RLRHDEIITL 130 140 150 160 170 180 LKNVGERVVL EVEYELPPPA PENNPRIISK TVDVSLYKEG NSFGFVLRGG AHEDLHKSRP 190 200 210 220 230 240 LVLTYVRPGG PADREGSLKV GDRLLSIDGI PLHGASHATA IATLQQCSHE ALFQVEYDVA 250 260 270 280 290 300 TPDTVANASG PLVVEIAKTP GSALGISLTT GSHRNKPAIT IDRIKPASVV DRSGALHAGD 310 320 330 340 350 360 HILAIDGTST EHCSLVEATK LLASVTEKVR LEILPAPQSR RPLKPPEAAV SSTPFSSPTM 370 380 390 400 410 420 NPAFPCANAS TLPRGPMSPR TTAGRRRQRR KEHRSSLSLA SSTVGPGGQI VHTETTEVVL 430 440 450 460 470 480 CGDPLSGFGL QLQGGIFATE TLSSPPLVRF IEPDSPAERC GLLQVGDRVL AINGIATEDG 490 500 510 520 530 540 TMEEANQLLR DAALARKVVL EIEFDVAESV IPSSGTFHVK LPKRRGVELG ITISSASRKR 550 560 570 580 590 600 GEPLIISDIK KGSVAHRTGT LEPGDKLLAI DNIRLDHCPM EYAVQILRQC EDLVKLKIRK 610 620 630 640 650 660 DEDNSDEQES SGAVSYTVEL KRYGGPLGIT ISGTEEPFDP IIISGLTKRG LAERTGAIHV 670 680 690 700 710 720 GDRILAINSV SLKGRPLSEA IHLLQVAGET VTLKIKKQLD RPLLPRQSGS LSEASDVDED 730 740 750 760 770 780 PPEALKGGLL TTHFSPAVPS VDSAVESWGS SATEGGFGGS GSYTPQVAVR SVTPQEWRSS 790 800 810 820 830 840 RLKSSPPPLE PRRTSYTPGP TDESFPEEEE GDWEPPMSPA PGPAREEGFW RVLGEALEDL 850 860 870 880 890 900 ESCGQSELLR ELEASIMTGT VQSVAVDGRP GSRPWRRSRE VGTSPEDLQE LLLPTPLEMH 910 920 930 940 950 960 RVTLHKDPVR NDFGFSVSDG LLEKGVYVHT VRIDGPAQHG GLQPFDRLLQ VNHVRTRDFD 970 980 990 1000 CCLAVPLLAE AGDILELVVS RNPLAQSRRT PGAPGPSSPQ MI
	Isoform 3 (ABP) (ABP-S). Checksum: EAA388ED9CA1425B	FASTA	822	88,314
	10 20 30 40 50 60 MVELIKREGS TLGLTISGGT DKDGKPRVSN LRPGGLAARS DLLNVGDYIR SVNGIRLTRL 70 80 90 100 110 120 RHDEIITLLK NVGERVVLEV EYELPPPAPE NNPRIISKTV DVSLYKEGNS FGFVLRGGAH 130 140 150 160 170 180 EDLHKSRPLV LTYVRPGGPA DREGSLKVGD RLLSIDGIPL HGASHATAIA TLQQCSHEAL 190 200 210 220 230 240 FQVEYDVATP DTVANASGPL VVEIAKTPGS ALGISLTTGS HRNKPAITID RIKPASVVDR 250 260 270 280 290 300 SGALHAGDHI LAIDGTSTEH CSLVEATKLL ASVTEKVRLE ILPAPQSRRP LKPPEAVRIQ 310 320 330 340 350 360 RSEQLHHWDP CVPSCHSPRP SHCRAPTWAP GGQDQSRSVS STPFSSPTMN PAFPCANAST 370 380 390 400 410 420 LPRGPMSPRT TAGRRRQRRK EHRSSLSLAS STVGPGGQIV HTETTEVVLC GDPLSGFGLQ 430 440 450 460 470 480 LQGGIFATET LSSPPLVRFI EPDSPAERCG LLQVGDRVLA INGIATEDGT MEEANQLLRD 490 500 510 520 530 540 AALARKVVLE IEFDVAESVI PSSGTFHVKL PKRRGVELGI TISSASRKRG EPLIISDIKK 550 560 570 580 590 600 GSVAHRTGTL EPGDKLLAID NIRLDHCPME YAVQILRQCE DLVKLKIRKD EDNSDEQESS 610 620 630 640 650 660 GAVSYTVELK RYGGPLGITI SGTEEPFDPI IISGLTKRGL AERTGAIHVG DRILAINSVS 670 680 690 700 710 720 LKGRPLSEAI HLLQVAGETV TLKIKKQLDR PLLPRQSGSL SEASDVDEDP PEALKGGLLT 730 740 750 760 770 780 THFSPAVPSV DSAVESWGSS ATEGGFGGSG SYTPQVAVRS VTPQEWRSSR LKSSPPPLEP 790 800 810 820 RRTSYTPGPT DESFPEEEEG DWEPPMRHPV SPLSTPSHLP LF
	Isoform 4 (pABP-L). Checksum: CC93D8A6451D2273	FASTA	1,043	112,550
	10 20 30 40 50 60 MRGWRRNLAL CLQRLPDEDD GPYSKGGKDT AGTDGALVCR RQSIPEEFRG ITMVELIKRE 70 80 90 100 110 120 GSTLGLTISG GTDKDGKPRV SNLRPGGLAA RSDLLNVGDY IRSVNGIRLT RLRHDEIITL 130 140 150 160 170 180 LKNVGERVVL EVEYELPPPA PENNPRIISK TVDVSLYKEG NSFGFVLRGG AHEDLHKSRP 190 200 210 220 230 240 LVLTYVRPGG PADREGSLKV GDRLLSIDGI PLHGASHATA IATLQQCSHE ALFQVEYDVA 250 260 270 280 290 300 TPDTVANASG PLVVEIAKTP GSALGISLTT GSHRNKPAIT IDRIKPASVV DRSGALHAGD 310 320 330 340 350 360 HILAIDGTST EHCSLVEATK LLASVTEKVR LEILPAPQSR RPLKPPEAVR IQRSEQLHHW 370 380 390 400 410 420 DPCVPSCHSP RPSHCRAPTW APGGQDQSRS VSSTPFSSPT MNPAFPCANA STLPRGPMSP 430 440 450 460 470 480 RTTAGRRRQR RKEHRSSLSL ASSTVGPGGQ IVHTETTEVV LCGDPLSGFG LQLQGGIFAT 490 500 510 520 530 540 ETLSSPPLVR FIEPDSPAER CGLLQVGDRV LAINGIATED GTMEEANQLL RDAALARKVV 550 560 570 580 590 600 LEIEFDVAES VIPSSGTFHV KLPKRRGVEL GITISSASRK RGEPLIISDI KKGSVAHRTG 610 620 630 640 650 660 TLEPGDKLLA IDNIRLDHCP MEYAVQILRQ CEDLVKLKIR KDEDNSDEQE SSGAVSYTVE 670 680 690 700 710 720 LKRYGGPLGI TISGTEEPFD PIIISGLTKR GLAERTGAIH VGDRILAINS VSLKGRPLSE 730 740 750 760 770 780 AIHLLQVAGE TVTLKIKKQL DRPLLPRQSG SLSEASDVDE DPPEALKGGL LTTHFSPAVP 790 800 810 820 830 840 SVDSAVESWG SSATEGGFGG SGSYTPQVAV RSVTPQEWRS SRLKSSPPPL EPRRTSYTPG 850 860 870 880 890 900 PTDESFPEEE EGDWEPPMSP APGPAREEGF WRVLGEALED LESCGQSELL RELEASIMTG 910 920 930 940 950 960 TVQSVAVDGR PGSRPWRRSR EVGTSPEDLQ ELLLPTPLEM HRVTLHKDPV RNDFGFSVSD 970 980 990 1000 1010 1020 GLLEKGVYVH TVRIDGPAQH GGLQPFDRLL QVNHVRTRDF DCCLAVPLLA EAGDILELVV 1030 1040 SRNPLAQSRR TPGAPGPSSP QMI

References

[1]	"Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP." Srivastava S., Osten P., Vilim F.S., Khatri L., Inman G., States B., Daly C., DeSouza S., Abagyan R., Valtschanoff J.G., Weinberg R.J., Ziff E.B. Neuron 21:581-591(1998) [PubMed: 9768844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, INTERACTION WITH GRIA2 AND GRIA3.
[2]	"EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains." Brueckner K., Pablo Labrador J., Scheiffele P., Herb A., Seeburg P.H., Klein R. Neuron 22:511-524(1999) [PubMed: 10197531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, INTERACTION WITH EFNB1 AND EFNB3. Tissue: Hippocampus.
[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: 10436050] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION. Tissue: Hippocampus.
[4]	"Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo." Wyszynski M., Valtschanoff J.G., Naisbitt S., Dunah A.W., Kim E., Standaert D.G., Weinberg R., Sheng M. J. Neurosci. 19:6528-6537(1999) [PubMed: 10414981] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, INTERACTION WITH GRIA2 AND GRIA3.
[5]	"Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters." DeSouza S., Fu J., States B.A., Ziff E.B. J. Neurosci. 22:3493-3503(2002) [PubMed: 11978826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PALMITOYLATION.
[6]	"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: 10896157] [Abstract] Cited for: INTERACTION WITH GRIPAP1.
[7]	"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: 12458226] [Abstract] Cited for: INTERACTION WITH CSGP4, DOMAIN.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF090113 mRNA. Translation: AAC36313.1. AF072509 mRNA. Translation: AAD25916.1. AF205193 mRNA. Translation: AAF19028.1. AF112182 mRNA. Translation: AAD28427.1. Different initiation.
IPI	IPI00197449. IPI00205556. IPI00409968. IPI00409970.
RefSeq	NP_612544.2.
UniGene	Rn.15680
3D structure databases
HSSP	HSSP built from PDB template 1M5Z based on UniProtKB P97879.
SMR	Q9WTW1. Positions 240-345, 450-644, 653-741, 935-1024.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9WTW1. 7 interactions.
PTM databases
PhosphoSite	Q9WTW1.
Genome annotation databases
Ensembl	ENSRNOG00000009726. Rattus norvegicus. [Contig view]
GeneID	171571.
KEGG	rno:171571.
Organism-specific databases
RGD	621668. Grip2.
Phylogenomic databases
HOVERGEN	Q9WTW1.
Gene expression databases
ArrayExpress	Q9WTW1.
GermOnline	ENSRNOG00000009726. Rattus norvegicus.
Family and domain databases
InterPro	IPR001478. PDZ/DHR/GLGF. [Graphical view]
Pfam	PF00595. PDZ. 7 hits. [Graphical view]
SMART	SM00228. PDZ. 7 hits. [Graphical view]
PROSITE	PS50106. PDZ. 7 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	622587.

Entry information

Entry name

GRIP2_RAT

Accession

Primary (citable) accession number: Q9WTW1
Secondary accession number(s): O88961, Q9WU36

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	November 1, 1999
Last modified:	June 16, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)