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Protein

Receptor of activated protein C kinase 1

Gene

RACK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Scaffolding protein 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 (PubMed:23636399). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843). 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. Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (PubMed:19674157). Promotes migration of breast carcinoma cells by binding to and activating RHOA (PubMed:20499158).21 Publications
(Microbial infection) Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells.1 Publication
(Microbial infection) Enhances phosphorylation of HIV-1 Nef by PKCs.1 Publication
(Microbial infection) In case of poxvirus infection, remodels the ribosomes so that they become optimal for the viral mRNAs (containing poly-A leaders) translation but not for host mRNAs.1 Publication
(Microbial infection) Contributes to the cap-independent internal ribosome entry site (IRES)-mediated translation by some RNA viruses.1 Publication

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • cyclin binding Source: UniProtKB
  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
  • enzyme binding Source: BHF-UCL
  • ion channel inhibitor activity Source: UniProtKB
  • protein-containing complex scaffold activity Source: BHF-UCL
  • protein homodimerization activity Source: ParkinsonsUK-UCL
  • protein kinase C binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • protein tyrosine kinase inhibitor activity Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB
  • ribosome binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • signaling adaptor activity Source: ParkinsonsUK-UCL
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cellular response to glucose stimulus Source: ParkinsonsUK-UCL
  • cellular response to growth factor stimulus Source: UniProtKB
  • gastrulation Source: UniProtKB-KW
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of endoplasmic reticulum unfolded protein response Source: ParkinsonsUK-UCL
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of hydrogen peroxide-induced neuron death Source: ParkinsonsUK-UCL
  • negative regulation of peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • negative regulation of phagocytosis Source: UniProtKB
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • pigmentation Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cAMP catabolic process Source: BHF-UCL
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of ceramide biosynthetic process Source: Reactome
  • positive regulation of cyclic-nucleotide phosphodiesterase activity Source: BHF-UCL
  • positive regulation of gastrulation Source: UniProtKB
  • positive regulation of Golgi to plasma membrane protein transport Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of mitochondrial depolarization Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • positive regulation of protein homooligomerization Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of cell cycle Source: UniProtKB
  • regulation of cell division Source: UniProtKB
  • regulation of establishment of cell polarity Source: UniProtKB
  • regulation of protein localization Source: UniProtKB
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • rescue of stalled ribosome Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionDevelopmental protein, Ribonucleoprotein, Ribosomal protein
Biological processApoptosis, Biological rhythms, Cell cycle, Gastrulation, Growth regulation, Host-virus interaction, Translation regulation

Enzyme and pathway databases

ReactomeiR-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5626978 TNFR1-mediated ceramide production
SignaLinkiP63244
SIGNORiP63244

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor of activated protein C kinase 1
Alternative name(s):
Cell proliferation-inducing gene 21 protein
Guanine nucleotide-binding protein subunit beta-2-like 1
Guanine nucleotide-binding protein subunit beta-like protein 12.3
Human lung cancer oncogene 7 protein
Short name:
HLC-7
Receptor for activated C kinase
Small ribosomal subunit protein RACK11 Publication
Cleaved into the following chain:
Alternative name(s):
Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed
Gene namesi
Name:RACK1Imported
Synonyms:GNB2L1
ORF Names:HLC7, PIG21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000204628.11
HGNCiHGNC:4399 RACK1
MIMi176981 gene
neXtProtiNX_P63244

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi36 – 38RDK → DDE in DEmut; abolishes association with the ribosome and ability to initiate the ribosome quality control (RQC). 1 Publication3
Mutagenesisi52Y → F: No effect on binding to SRC. Abolishes binding to PTK2/FAK1 and reduces cell adhesion and foci formation. 3 Publications1
Mutagenesisi57R → A: Decreased binding to PTK2/FAK1; when associated with A-60. 1 Publication1
Mutagenesisi60R → A: Decreased binding to PTK2/FAK1; when associated with A-57. 1 Publication1
Mutagenesisi127K → A: Decreased binding to PTK2/FAK1; when associated with A-130. 1 Publication1
Mutagenesisi130K → A: Decreased binding to PTK2/FAK1; when associated with A-127. 1 Publication1
Mutagenesisi140Y → F: No effect on binding to SRC. 2 Publications1
Mutagenesisi194Y → F: No effect on binding to SRC. 2 Publications1
Mutagenesisi228Y → F: No effect on binding to SRC. Does not abolish phosphorylation by SRC. Abolishes phosphorylation by SRC; when associated with F-246 and F-302. 2 Publications1
Mutagenesisi246Y → F: Abolishes binding to SRC. Does not abolish phosphorylation by SRC. Abolishes phosphorylation by SRC; when associated with F-228 and F-302. 2 Publications1
Mutagenesisi276 – 279STSS → EEEE: Enhanced translation of mRNAs containing poly-A leaders. 1 Publication4
Mutagenesisi278S → E: Enhanced translation of mRNAs containing poly-A leaders. 1 Publication1
Mutagenesisi302Y → F: No effect on binding to SRC. Abolishes phosphorylation by SRC; when associated with F-228 and F-246. 2 Publications1

Organism-specific databases

DisGeNETi10399
OpenTargetsiENSG00000204628
PharmGKBiPA28779

Polymorphism and mutation databases

BioMutaiGNB2L1
DMDMi54037168

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004244801 – 317Receptor of activated protein C kinase 1Add BLAST317
Initiator methionineiRemoved; alternateCombined sources1 Publication
ChainiPRO_00001277312 – 317Receptor of activated protein C kinase 1, N-terminally processedAdd BLAST316

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei2N-acetylthreonine; in Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processedCombined sources1 Publication1
Modified residuei6PhosphothreonineCombined sources1
Modified residuei10PhosphothreonineCombined sources1
Modified residuei52Phosphotyrosine; by ABL11 Publication1
Modified residuei96PhosphothreonineCombined sources1
Modified residuei130N6-acetyllysineCombined sources1
Modified residuei183N6-acetyllysineBy similarity1
Modified residuei228Phosphotyrosine1 Publication1
Modified residuei276Phosphoserine; by viral VacV B1 kinaseCombined sources1 Publication1
Modified residuei277Phosphothreonine; by viral VacV B1 kinase1 Publication1
Modified residuei278Phosphoserine; by viral VacV B1 kinase1 Publication1
Modified residuei279Phosphoserine; by viral VacV B1 kinase1 Publication1
Modified residuei316PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated on Tyr-228 and/or Tyr-246 by SRC. This is required for binding to SRC.3 Publications
(Microbial infection) Phosphorylated by vaccinia virus B1 kinase on serine and threonine residues; this phosphorylation remodels the ribosome properties, favoring the viral mRNA translation.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP63244
MaxQBiP63244
PaxDbiP63244
PeptideAtlasiP63244
PRIDEiP63244
ProteomicsDBi57512
TopDownProteomicsiP63244

2D gel databases

REPRODUCTION-2DPAGEiIPI00848226
P63244

PTM databases

iPTMnetiP63244
PhosphoSitePlusiP63244
SwissPalmiP63244

Expressioni

Tissue specificityi

In the liver, expressed at higher levels in activated hepatic stellate cells than in hepatocytes or Kupffer cells. Up-regulated in hepatocellular carcinomas and in the adjacent non-tumor liver tissue.1 Publication

Gene expression databases

BgeeiENSG00000204628
CleanExiHS_GNB2L1
ExpressionAtlasiP63244 baseline and differential
GenevisibleiP63244 HS

Organism-specific databases

HPAiCAB004288
HPA021676

Interactioni

Subunit structurei

Monomer; also forms homodimers and homooligomers (PubMed:20529362, PubMed:15140893). Interacts with CPNE3 (PubMed:20010870). May interact with ABCB4 (PubMed:19674157). Component of the small (40S) ribosomal subunit (By similarity). Interacts with the 80S ribosome (PubMed:23636399). 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 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 TBXA2R isoform 2. Interacts with HRAS. Interacts with LARP4B. Interacts with LARP4 (PubMed:21098120). Interacts with PKD2L1.By similarity28 Publications
(Microbial infection) Interacts with Y.pseudotuberculosis yopK.1 Publication
(Microbial infection) Interacts with Y.pseudotuberculosis yopK. Interacts with a number of viral proteins including Epstein-Barr virus BZLF1 and HIV-1 Nef; interaction with Nef increases Nef phosphorylation by PKC.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • cyclin binding Source: UniProtKB
  • enzyme binding Source: BHF-UCL
  • protein-containing complex scaffold activity Source: BHF-UCL
  • protein homodimerization activity Source: ParkinsonsUK-UCL
  • protein kinase C binding Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115671, 216 interactors
CORUMiP63244
DIPiDIP-46736N
IntActiP63244, 102 interactors
MINTiP63244
STRINGi9606.ENSP00000426909

Structurei

Secondary structure

1317
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 11Combined sources8
Beta strandi18 – 23Combined sources6
Beta strandi30 – 35Combined sources6
Beta strandi40 – 45Combined sources6
Beta strandi48 – 50Combined sources3
Beta strandi52 – 59Combined sources8
Beta strandi66 – 71Combined sources6
Beta strandi75 – 82Combined sources8
Beta strandi85 – 91Combined sources7
Turni92 – 95Combined sources4
Beta strandi96 – 102Combined sources7
Beta strandi108 – 113Combined sources6
Beta strandi120 – 124Combined sources5
Beta strandi129 – 132Combined sources4
Beta strandi138 – 142Combined sources5
Beta strandi144 – 146Combined sources3
Beta strandi151 – 156Combined sources6
Beta strandi160 – 162Combined sources3
Beta strandi164 – 169Combined sources6
Beta strandi174 – 178Combined sources5
Turni179 – 182Combined sources4
Beta strandi183 – 188Combined sources6
Beta strandi195 – 200Combined sources6
Beta strandi204 – 211Combined sources8
Beta strandi215 – 220Combined sources6
Turni221 – 224Combined sources4
Beta strandi225 – 231Combined sources7
Beta strandi236 – 241Combined sources6
Beta strandi243 – 252Combined sources10
Beta strandi255 – 260Combined sources6
Turni261 – 264Combined sources4
Beta strandi265 – 270Combined sources6
Beta strandi286 – 291Combined sources6
Beta strandi295 – 302Combined sources8
Beta strandi307 – 313Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4AOWX-ray2.45A/B/C1-317[»]
4UG0electron microscopy-Sg1-317[»]
4V6Xelectron microscopy5.00Ag1-317[»]
5A2Qelectron microscopy3.90g1-315[»]
5AJ0electron microscopy3.50Bg1-317[»]
5FLXelectron microscopy3.90g1-317[»]
5LKSelectron microscopy3.60Sg1-317[»]
5OA3electron microscopy4.30g1-315[»]
5T2Celectron microscopy3.60AI1-317[»]
5VYCX-ray6.00g1/g2/g3/g4/g5/g61-317[»]
6EK0electron microscopy2.90Sg1-317[»]
6FECelectron microscopy6.30m2-314[»]
ProteinModelPortaliP63244
SMRiP63244
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati13 – 44WD 1Add BLAST32
Repeati61 – 91WD 2Add BLAST31
Repeati103 – 133WD 3Add BLAST31
Repeati146 – 178WD 4Add BLAST33
Repeati190 – 220WD 5Add BLAST31
Repeati231 – 260WD 6Add BLAST30
Repeati281 – 311WD 7Add BLAST31

Domaini

The 7 WD repeats mediate protein-protein interactions with binding partners.1 Publication

Sequence similaritiesi

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0279 Eukaryota
ENOG410XQGZ LUCA
GeneTreeiENSGT00910000144232
HOVERGENiHBG000277
InParanoidiP63244
KOiK14753
OMAiQYGYPKR
PhylomeDBiP63244
TreeFamiTF300600

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR020472 G-protein_beta_WD-40_rep
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF00400 WD40, 7 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 4 hits
PS50082 WD_REPEATS_2, 6 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P63244-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEQMTLRGT LKGHNGWVTQ IATTPQFPDM ILSASRDKTI IMWKLTRDET
60 70 80 90 100
NYGIPQRALR GHSHFVSDVV ISSDGQFALS GSWDGTLRLW DLTTGTTTRR
110 120 130 140 150
FVGHTKDVLS VAFSSDNRQI VSGSRDKTIK LWNTLGVCKY TVQDESHSEW
160 170 180 190 200
VSCVRFSPNS SNPIIVSCGW DKLVKVWNLA NCKLKTNHIG HTGYLNTVTV
210 220 230 240 250
SPDGSLCASG GKDGQAMLWD LNEGKHLYTL DGGDIINALC FSPNRYWLCA
260 270 280 290 300
ATGPSIKIWD LEGKIIVDEL KQEVISTSSK AEPPQCTSLA WSADGQTLFA
310
GYTDNLVRVW QVTIGTR
Length:317
Mass (Da):35,077
Last modified:January 23, 2007 - v3
Checksum:i257F91E369ED2044
GO

Sequence cautioni

The sequence AAO21313 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAR24619 differs from that shown. Reason: Frameshift at position 94.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti70 – 111Missing in BAG53102 (PubMed:14702039).CuratedAdd BLAST42
Sequence conflicti94T → TRK in AAR24619 (Ref. 3) Curated1
Sequence conflicti221L → F in BAD96208 (Ref. 6) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24194 mRNA Translation: AAA59626.1
AY159316 mRNA Translation: AAO21313.1 Different initiation.
AY336089 mRNA Translation: AAR24619.1 Frameshift.
AK095666 mRNA Translation: BAG53102.1
CR456978 mRNA Translation: CAG33259.1
CR541909 mRNA Translation: CAG46707.1
AK222488 mRNA Translation: BAD96208.1
CH471165 Genomic DNA Translation: EAW53692.1
CH471165 Genomic DNA Translation: EAW53702.1
BC000214 mRNA Translation: AAH00214.1
BC000366 mRNA Translation: AAH00366.1
BC010119 mRNA Translation: AAH10119.1
BC014256 mRNA Translation: AAH14256.1
BC014788 mRNA Translation: AAH14788.1
BC017287 mRNA Translation: AAH17287.1
BC019093 mRNA Translation: AAH19093.1
BC019362 mRNA Translation: AAH19362.1
BC021993 mRNA Translation: AAH21993.1
BC032006 mRNA Translation: AAH32006.1
CCDSiCCDS34324.1
PIRiB33928
RefSeqiNP_006089.1, NM_006098.4
UniGeneiHs.5662

Genome annotation databases

EnsembliENST00000512805; ENSP00000426909; ENSG00000204628
GeneIDi10399
KEGGihsa:10399
UCSCiuc003mni.2 human

Similar proteinsi

Entry informationi

Entry nameiRACK1_HUMAN
AccessioniPrimary (citable) accession number: P63244
Secondary accession number(s): B3KTJ0
, D3DWS0, P25388, P99049, Q53HU2, Q5J8M6, Q5VLR4, Q6FH47
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 151 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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