P68040 (GBLP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanine nucleotide-binding protein subunit beta-2-like 1

Alternative name(s):
12-3
Receptor for activated C kinase
Receptor of activated protein kinase C 1
Short name=RACK1
p205

Gene names

Name:	Gnb2l1
Synonyms:	Gnb2-rs1

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	317 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression. Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Ref.1 Ref.11 Ref.12
Subunit structure	Component of the small (40S) ribosomal subunit. Interacts with LARP4B By similarity. Exists as a monomer and also forms oligomers. Binds SLC9A3R1. Forms a ternary complex with TRIM63 and PRKCE. Interacts with HABP4, KRT1 and OTUB1. Interacts with SRC (via SH2 domain); the interaction is enhanced by tyrosine phosphorylation of GNB2L1/RACK1. Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and PRKCA. Interacts with AR. Interacts with IGF1R but not with INSR. Interacts with ADAM12. Interacts with CLEC1B (via N-terminal region) and with HIF1A; the interaction promotes their degradation. Interacts with RHOA; this enhances RHOA activation and promotes cell migration. Interacts with CHRM2; the interaction regulates CHRM2 internalization. Interacts with TRPM6 (via kinase domain). Interacts with PTK2/FAK1; required for PTK2/FAK1 phosphorylation and dephosphorylation. Interacts with FLT1. Interacts with HRAS. Ref.11 Ref.12 Ref.13
Subcellular location	Cell membrane; Peripheral membrane protein By similarity. Cytoplasm By similarity. Cytoplasm › perinuclear region By similarity. Cytoplasm › cytoskeleton By similarity. Nucleus. Perikaryon. Cell projection › dendrite. Note: Recruited to the plasma membrane through interaction with KRT1 which binds to membrane-bound ITGB1. PKC activation induces translocation from the perinuclear region to the cell periphery. In the brain, detected mainly in cell bodies and dendrites with little expression in axonal fibers or nuclei By similarity. Ref.10 Ref.12
Tissue specificity	Strongly and ubiquitously expressed in the embryonic and early postnatal brain. At E11.5, expressed in a high-dorsal to low-ventral gradient throughout the brain. At E13.5, most abundant in the telecephalon. At E18.5, expressed most abundantly in layers 1-4 of the cortex, striatum, hippocampus, dentate gyrus, and specific thalamic nuclei. This expression decreases during postnatal development and is localized in the dentate gyrus, habenula, piriform cortex, paraventricular nucleus of the hypothalamus and supraoptic nucleus of the adult brain. Ref.1 Ref.10
Developmental stage	Expressed throughout embryonic brain development with high levels detected at E11.5, E13.5 and E18.5. Also detected at high levels in the adult brain. Ref.10
Post-translational modification	Phosphorylated on Tyr-228 and/or Tyr-246 by SRC. This is required for binding to SRC By similarity.
Sequence similarities	Belongs to the WD repeat G protein beta family. Contains 7 WD repeats.
Sequence caution	The sequence AAG29506.1 differs from that shown. Reason: Frameshift at positions 232 and 239.

Ontologies

Keywords
Biological process	Apoptosis Biological rhythms Cell cycle Gastrulation Growth regulation Translation regulation
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Nucleus
Domain	Repeat WD repeat
Molecular function	Developmental protein
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW gastrulation Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from sequence alignment PubMed 11099474. Source: MGI negative regulation of Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of phagocytosis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara negative regulation of translation Inferred from electronic annotation. Source: Compara positive regulation of GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of gastrulation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of intrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein homooligomerization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein localization Inferred from sequence alignment PubMed 11099474. Source: MGI regulation of cell cycle Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell division Inferred from sequence or structural similarity. Source: UniProtKB regulation of establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB regulation of establishment of protein localization to plasma membrane Inferred from electronic annotation. Source: Compara regulation of protein localization Inferred from sequence or structural similarity. Source: UniProtKB rhythmic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell dendrite Inferred from direct assay Ref.10. Source: UniProtKB midbody Inferred from sequence or structural similarity. Source: UniProtKB neuronal cell body Inferred from direct assay Ref.10. Source: MGI nucleus Inferred from sequence or structural similarity. Source: UniProtKB perikaryon Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB phagocytic cup Inferred from sequence or structural similarity. Source: UniProtKB small ribosomal subunit Inferred from electronic annotation. Source: Compara
Molecular_function	SH2 domain binding Inferred from sequence or structural similarity. Source: UniProtKB cysteine-type endopeptidase activator activity involved in apoptotic process Inferred from electronic annotation. Source: Compara ion channel inhibitor activity Inferred from direct assay Ref.11. Source: UniProtKB protein kinase C binding Inferred from sequence or structural similarity. Source: UniProtKB protein tyrosine kinase inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB receptor activity Inferred from sequence alignment PubMed 11099474. Source: MGI receptor tyrosine kinase binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ikbkb	O88351	4	EBI-296749,EBI-447960

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 317	316	Guanine nucleotide-binding protein subunit beta-2-like 1		PRO_0000127732
Regions
	Repeat	13 – 44	32	WD 1
	Repeat	61 – 91	31	WD 2
	Repeat	103 – 133	31	WD 3
	Repeat	146 – 178	33	WD 4
	Repeat	190 – 220	31	WD 5
	Repeat	231 – 260	30	WD 6
	Repeat	281 – 311	31	WD 7
Amino acid modifications
	Modified residue	2	1	N-acetylthreonine Ref.8
	Modified residue	52	1	Phosphotyrosine; by ABL1 By similarity
	Modified residue	130	1	N6-acetyllysine By similarity
	Modified residue	228	1	Phosphotyrosine By similarity
Experimental info
	Sequence conflict	9	1	G → R in BAE40068. Ref.3
	Sequence conflict	9	1	G → R in BAE40156. Ref.3
	Sequence conflict	125	1	R → Q in BAE40059. Ref.3
	Sequence conflict	125	1	R → Q in BAE40068. Ref.3
	Sequence conflict	125	1	R → Q in BAE40156. Ref.3
	Sequence conflict	248	1	L → P in BAE35378. Ref.3
	Sequence conflict	266	1	I → M in AAG29506. Ref.6
	Sequence conflict	273	1	E → A in BAA06185. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P68040 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 257F91E369ED2044	FASTA	317	35,077
	10 20 30 40 50 60 MTEQMTLRGT LKGHNGWVTQ IATTPQFPDM ILSASRDKTI IMWKLTRDET NYGIPQRALR 70 80 90 100 110 120 GHSHFVSDVV ISSDGQFALS GSWDGTLRLW DLTTGTTTRR FVGHTKDVLS VAFSSDNRQI 130 140 150 160 170 180 VSGSRDKTIK LWNTLGVCKY TVQDESHSEW VSCVRFSPNS SNPIIVSCGW DKLVKVWNLA 190 200 210 220 230 240 NCKLKTNHIG HTGYLNTVTV SPDGSLCASG GKDGQAMLWD LNEGKHLYTL DGGDIINALC 250 260 270 280 290 300 FSPNRYWLCA ATGPSIKIWD LEGKIIVDEL KQEVISTSSK AEPPQCTSLA WSADGQTLFA 310 GYTDNLVRVW QVTIGTR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a neural differentiation-associated gene, p205, in the embryonal carcinoma cell line P19 and in the developing mouse." Imai Y., Suzuki Y., Tohyama M., Wanaka A., Takagi T. Brain Res. Mol. Brain Res. 24:313-319(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]	"Primary sequence of the mouse guanine nucleotide binding protein related gene." Raj N.B.K., Su Y., Au W.C., Pitha P.M. Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Spleen.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: BALB/c, C57BL/6J and DBA/2. Tissue: Blastocyst, Embryo, Embryonic head, Embryonic spinal ganglion, Embryonic stem cell, Head, Kidney, Mammary gland and Osteoclast.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[7]	"Genomic structure and expression of mouse receptor for activated C kinase (RACK1)." Choi D., Messing R.O. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-296. Strain: 129/SvJ.
[8]	Kanor S., Quadroni M., Bienvenut W.V. Submitted (MAR-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11 AND 271-279, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, MASS SPECTROMETRY. Strain: C57BL/6J. Tissue: Skeletal muscle.
[9]	Lubec G., Klug S., Yang J.W., Zigmond M. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 226-317, MASS SPECTROMETRY. Tissue: Brain and Hippocampus.
[10]	"Localization of the scaffolding protein RACK1 in the developing and adult mouse brain." Ashique A.M., Kharazia V., Yaka R., Phamluong K., Peterson A.S., Ron D. Brain Res. 1069:31-38(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[11]	"RACK1 inhibits TRPM6 activity via phosphorylation of the fused alpha-kinase domain." Cao G., Thebault S., van der Wijst J., van der Kemp A., Lasonder E., Bindels R.J., Hoenderop J.G. Curr. Biol. 18:168-176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TRPM6.
[12]	"Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock." Robles M.S., Boyault C., Knutti D., Padmanabhan K., Weitz C.J. Science 327:463-466(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BMAL1 AND PRKCA, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[13]	"Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity." Li S., Esterberg R., Lachance V., Ren D., Radde-Gallwitz K., Chi F., Parent J.L., Fritz A., Chen P. Proc. Natl. Acad. Sci. U.S.A. 108:2264-2269(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VANGL2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D29802 mRNA. Translation: BAA06185.1. X75313 mRNA. Translation: CAA53062.1. AK002493 mRNA. Translation: BAB22141.1. AK012242 mRNA. Translation: BAB28114.1. AK017772 mRNA. Translation: BAB30920.1. AK051226 mRNA. Translation: BAC34564.1. AK159797 mRNA. Translation: BAE35378.1. AK160528 mRNA. Translation: BAE35846.1. AK160739 mRNA. Translation: BAE35980.1. AK161234 mRNA. Translation: BAE36257.1. AK166417 mRNA. Translation: BAE38762.1. AK166786 mRNA. Translation: BAE39017.1. AK166800 mRNA. Translation: BAE39028.1. AK166889 mRNA. Translation: BAE39095.1. AK166945 mRNA. Translation: BAE39133.1. AK168086 mRNA. Translation: BAE40059.1. AK168096 mRNA. Translation: BAE40068.1. AK168196 mRNA. Translation: BAE40156.1. AK168349 mRNA. Translation: BAE40286.1. AL645849 Genomic DNA. Translation: CAI35106.1. CH466575 Genomic DNA. Translation: EDL33791.1. BC046760 mRNA. Translation: AAH46760.1. AF295529 Genomic DNA. Translation: AAG29506.1. Frameshift.
IPI	IPI00317740.
PIR	S38398.
RefSeq	NP_032169.1. NM_008143.3.
UniGene	Mm.5305.
3D structure databases
ProteinModelPortal	P68040.
ModBase	Search...
Protein-protein interaction databases
IntAct	P68040. 10 interactions.
2D gel databases
REPRODUCTION-2DPAGE	P68040.
SWISS-2DPAGE	P68040.
Proteomic databases
PaxDb	P68040.
PRIDE	P68040.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020640; ENSMUSP00000020640; ENSMUSG00000020372.
GeneID	14694.
KEGG	mmu:14694.
UCSC	uc007ipa.1. mouse.
Organism-specific databases
CTD	10399.
MGI	MGI:101849. Gnb2l1.
Phylogenomic databases
eggNOG	COG2319.
GeneTree	ENSGT00700000104461.
HOVERGEN	HBG000277.
InParanoid	Q9CSQ0.
KO	K14753.
OMA	IRVWQVM.
OrthoDB	EOG4933J5.
Gene expression databases
Bgee	P68040.
Genevestigator	P68040.
GermOnline	ENSMUSG00000020372. Mus musculus.
Family and domain databases
Gene3D	2.130.10.10. 2 hits.
InterPro	IPR020472. G-protein_beta_WD-40_rep. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF00400. WD40. 7 hits. [Graphical view]
PRINTS	PR00320. GPROTEINBRPT.
SMART	SM00320. WD40. 7 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. 4 hits. PS50082. WD_REPEATS_2. 6 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GNB2L1. mouse.
NextBio	286639.
SOURCE	Search...

Entry information

Entry name

GBLP_MOUSE

Accession

Primary (citable) accession number: P68040
Secondary accession number(s): P25388 , P99049, Q3THP0, Q3THY7, Q3TKQ0, Q3TW88, Q5NCC5, Q5NCC6, Q9CSQ0, Q9ERM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program