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UniProtKB - O75582 (KS6A5_HUMAN)

Entry version 194 (03 Jul 2019)
Sequence version 1 (01 Nov 1998)
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Protein

Ribosomal protein S6 kinase alpha-5

Gene

RPS6KA5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:9687510, PubMed:18511904, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810).By similarity10 Publications

Miscellaneous

Enzyme activity requires the presence of both kinase domains.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei81ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei177Proton acceptorBy similarity1
Binding sitei455ATPPROSITE-ProRule annotation1
Active sitei544Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi55 – 63ATPPROSITE-ProRule annotation9
Nucleotide bindingi432 – 440ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processInflammatory response, Stress response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-198753 ERK/MAPK targets
R-HSA-199920 CREB phosphorylation
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-437239 Recycling pathway of L1
R-HSA-5621575 CD209 (DC-SIGN) signaling

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		O75582

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		O75582

SIGNOR Signaling Network Open Resource

More...SIGNORi		O75582

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Ribosomal protein S6 kinase alpha-5 (EC:2.7.11.1)
Short name:
S6K-alpha-5
Alternative name(s):
90 kDa ribosomal protein S6 kinase 5
Nuclear mitogen- and stress-activated protein kinase 1
RSK-like protein kinase
Short name:
RSKL
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:RPS6KA5
Synonyms:MSK1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Unplaced

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:10434 RPS6KA5

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603607 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O75582

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi195D → A: Loss of kinase activity. 1 Publication1
Mutagenesisi212S → A: Inactivates the N-terminal kinase domain. 1 Publication1
Mutagenesisi360S → A: Decreases kinase activity by 60% in response to PMA and UV-C. 1 Publication1
Mutagenesisi376S → A: Loss of kinase activity, and decreases the phosphorylation of S-360 and T-581. 1 Publication1
Mutagenesisi565D → A: Loss of kinase activity. 1 Publication1
Mutagenesisi581T → A: Loss of kinase activity, and blocks phosphorylation of S-212; S-376 and S-381 in response to PMA and UV-C. 1 Publication1
Mutagenesisi700T → A or D: Strongly reduces phosphorylation of T-581 in response to PMA and UV-C. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		9252

Open Targets

More...OpenTargetsi		ENSG00000100784

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA34849

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4237

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1523

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		RPS6KA5

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000862071 – 802Ribosomal protein S6 kinase alpha-5Add BLAST802

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei212Phosphoserine; by autocatalysis1 Publication1
Modified residuei360Phosphoserine; by MAPK1, MAPK3 and MAPK141 Publication1
Modified residuei376Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei381Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei581Phosphothreonine; by MAPK1, MAPK3 and MAPK141 Publication1
Modified residuei647Phosphoserine1 Publication1
Modified residuei657Phosphoserine1 Publication1
Modified residuei691PhosphoserineBy similarity1
Modified residuei695Phosphoserine1 Publication1
Modified residuei700Phosphothreonine; by MAPK1, MAPK3 and MAPK141 Publication1
Modified residuei750Phosphoserine; by autocatalysis1 Publication1
Modified residuei752Phosphoserine; by autocatalysis1 Publication1
Modified residuei758Phosphoserine; by autocatalysis1 Publication1
Modified residuei798PhosphoserineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain.2 Publications
Ubiquitinated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		O75582

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		O75582

MaxQB - The MaxQuant DataBase

More...MaxQBi		O75582

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		O75582

PeptideAtlas

More...PeptideAtlasi		O75582

PRoteomics IDEntifications database

More...PRIDEi		O75582

ProteomicsDB human proteome resource

More...ProteomicsDBi		50098
50099 [O75582-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O75582

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		O75582

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000100784 Expressed in 235 organ(s), highest expression level in caudate nucleus

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		O75582 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O75582 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB025458
HPA001274
HPA001780

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA.

Interacts with CREBBP and EP300.

2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		114676, 55 interactors

Database of interacting proteins

More...DIPi		DIP-30894N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		O75582

Protein interaction database and analysis system

More...IntActi		O75582, 38 interactors

Molecular INTeraction database

More...MINTi		O75582

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000479667

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O75582

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1802
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		O75582

Database of comparative protein structure models

More...ModBasei		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		O75582

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini49 – 318Protein kinase 1PROSITE-ProRule annotationAdd BLAST270
Domaini319 – 387AGC-kinase C-terminalAdd BLAST69
Domaini426 – 687Protein kinase 2PROSITE-ProRule annotationAdd BLAST262

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0598 Eukaryota
ENOG410XNPH LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000156886

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000233033

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O75582

KEGG Orthology (KO)

More...KOi		K04445

Identification of Orthologs from Complete Genome Data

More...OMAi		FQSHDKS

Database of Orthologous Groups

More...OrthoDBi		181575at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O75582

TreeFam database of animal gene trees

More...TreeFami		TF313438

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016239 Ribosomal_S6_kinase_II
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00069 Pkinase, 2 hits
PF00433 Pkinase_C, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF000606 Ribsml_S6_kin_2, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 2 hits

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112 SSF56112, 2 hits

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 2 hits
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00108 PROTEIN_KINASE_ST, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O75582-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AEKVGIENFE 
        60         70         80         90        100
LLKVLGTGAY GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT 
       110        120        130        140        150
ERQVLEHIRQ SPFLVTLHYA FQTETKLHLI LDYINGGELF THLSQRERFT 
       160        170        180        190        200
EHEVQIYVGE IVLALEHLHK LGIIYRDIKL ENILLDSNGH VVLTDFGLSK 
       210        220        230        240        250
EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS LGVLMYELLT 
       260        270        280        290        300
GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QRLLMKDPKK 
       310        320        330        340        350
RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE 
       360        370        380        390        400
EFTEMDPTYS PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMGV 
       410        420        430        440        450
ERPGVTNVAR SAMMKDSPFY QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ 
       460        470        480        490        500
AFAVKIISKR MEANTQKEIT ALKLCEGHPN IVKLHEVFHD QLHTFLVMEL 
       510        520        530        540        550
LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV VHRDLKPENL 
       560        570        580        590        600
LFTDENDNLE IKIIDFGFAR LKPPDNQPLK TPCFTLHYAA PELLNQNGYD 
       610        620        630        640        650
ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG 
       660        670        680        690        700
EAWKNVSQEA KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT 
       710        720        730        740        750
PDILGSSGAA VHTCVKATFH AFNKYKREGF CLQNVDKAPL AKRRKMKKTS 
       760        770        780        790        800
TSTETRSSSS ESSHSSSSHS HGKTTPTKTL QPSNPADSNN PETLFQFSDS 

VA
Length:802
Mass (Da):89,865
Last modified:November 1, 1998 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i76C27D0F6639BFA4
GO
Isoform 2 (identifier: O75582-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     549-549: N → V
     550-802: Missing.

Show »
Length:549
Mass (Da):61,769
Checksum:i3CED0A0C50E96C78
GO
Isoform 3 (identifier: O75582-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.

Note: No experimental confirmation available.
Show »
Length:723
Mass (Da):81,780
Checksum:i19C49A91CAAA0CBF
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V2D1G3V2D1_HUMAN
Ribosomal protein S6 kinase alpha-5
RPS6KA5
219Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A3B3ISL8A0A3B3ISL8_HUMAN
Ribosomal protein S6 kinase alpha-5
RPS6KA5
207Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YJE1H0YJE1_HUMAN
Ribosomal protein S6 kinase alpha-5
RPS6KA5
79Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
G3V4D7G3V4D7_HUMAN
Ribosomal protein S6 kinase alpha-5
RPS6KA5
83Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAC69577 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti452 – 453FA → LQ in AAC69577 (PubMed:10702687).Curated2
Sequence conflicti532V → L in AAC69577 (PubMed:10702687).Curated1
Sequence conflicti538V → L in AAC69577 (PubMed:10702687).Curated1
Sequence conflicti757 – 758SS → RG in AAC69577 (PubMed:10702687).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_051634190H → R. Corresponds to variant dbSNP:rs34699345Ensembl.1
Natural variantiVAR_040634554D → N1 PublicationCorresponds to variant dbSNP:rs55911249Ensembl.1
Natural variantiVAR_040635574P → L1 PublicationCorresponds to variant dbSNP:rs34604933Ensembl.1
Natural variantiVAR_040636599Y → C1 PublicationCorresponds to variant dbSNP:rs55968863Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0574101 – 79Missing in isoform 3. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_041837549N → V in isoform 2. 1 Publication1
Alternative sequenceiVSP_041838550 – 802Missing in isoform 2. 1 PublicationAdd BLAST253

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF074393 mRNA Translation: AAC31171.1
AF080000 mRNA Translation: AAD23915.1
AF090421 mRNA Translation: AAC69577.1 Frameshift.
AK295266 mRNA Translation: BAH12021.1
AL121784 Genomic DNA No translation available.
AL133454 Genomic DNA No translation available.
AL159191 Genomic DNA No translation available.
BC017187 mRNA Translation: AAH17187.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS45149.1 [O75582-2]
CCDS81839.1 [O75582-3]
CCDS9893.1 [O75582-1]

Protein sequence database of the Protein Information Resource

More...PIRi		T13149

NCBI Reference Sequences

More...RefSeqi		NP_001309164.1, NM_001322235.1 [O75582-3]
NP_001309166.1, NM_001322237.1 [O75582-3]
NP_004746.2, NM_004755.3 [O75582-1]
NP_872198.1, NM_182398.2 [O75582-2]

Genome annotation databases

Database of genes from NCBI RefSeq genomes

More...GeneIDi		9252

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:9252

UCSC genome browser

More...UCSCi		uc001xys.4 human [O75582-1]
uc010twi.3 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074393 mRNA Translation: AAC31171.1
AF080000 mRNA Translation: AAD23915.1
AF090421 mRNA Translation: AAC69577.1 Frameshift.
AK295266 mRNA Translation: BAH12021.1
AL121784 Genomic DNA No translation available.
AL133454 Genomic DNA No translation available.
AL159191 Genomic DNA No translation available.
BC017187 mRNA Translation: AAH17187.1
CCDSiCCDS45149.1 [O75582-2]
CCDS81839.1 [O75582-3]
CCDS9893.1 [O75582-1]
PIRiT13149
RefSeqiNP_001309164.1, NM_001322235.1 [O75582-3]
NP_001309166.1, NM_001322237.1 [O75582-3]
NP_004746.2, NM_004755.3 [O75582-1]
NP_872198.1, NM_182398.2 [O75582-2]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VZOX-ray1.80A2-348[»]
3KN5X-ray2.40A/B414-738[»]
3KN6X-ray2.00A/B414-738[»]
SMRiO75582
ModBaseiSearch...

Protein-protein interaction databases

BioGridi114676, 55 interactors
DIPiDIP-30894N
ELMiO75582
IntActiO75582, 38 interactors
MINTiO75582
STRINGi9606.ENSP00000479667

Chemistry databases

BindingDBiO75582
ChEMBLiCHEMBL4237
GuidetoPHARMACOLOGYi1523

PTM databases

iPTMnetiO75582
PhosphoSitePlusiO75582

Polymorphism and mutation databases

BioMutaiRPS6KA5

Proteomic databases

EPDiO75582
jPOSTiO75582
MaxQBiO75582
PaxDbiO75582
PeptideAtlasiO75582
PRIDEiO75582
ProteomicsDBi50098
50099 [O75582-2]

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		9252
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi9252
KEGGihsa:9252
UCSCiuc001xys.4 human [O75582-1]
uc010twi.3 human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		9252
DisGeNETi9252

GeneCards: human genes, protein and diseases

More...GeneCardsi		RPS6KA5
HGNCiHGNC:10434 RPS6KA5
HPAiCAB025458
HPA001274
HPA001780
MIMi603607 gene
neXtProtiNX_O75582
OpenTargetsiENSG00000100784
PharmGKBiPA34849

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00940000156886
HOGENOMiHOG000233033
InParanoidiO75582
KOiK04445
OMAiFQSHDKS
OrthoDBi181575at2759
PhylomeDBiO75582
TreeFamiTF313438

Enzyme and pathway databases

ReactomeiR-HSA-198753 ERK/MAPK targets
R-HSA-199920 CREB phosphorylation
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-437239 Recycling pathway of L1
R-HSA-5621575 CD209 (DC-SIGN) signaling
SABIO-RKiO75582
SignaLinkiO75582
SIGNORiO75582

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		RPS6KA5 human
EvolutionaryTraceiO75582

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		RPS6KA5

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		9252

Protein Ontology

More...PROi		PR:O75582

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000100784 Expressed in 235 organ(s), highest expression level in caudate nucleus
ExpressionAtlasiO75582 baseline and differential
GenevisibleiO75582 HS

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016239 Ribosomal_S6_kinase_II
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000606 Ribsml_S6_kin_2, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 2 hits
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 2 hits
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00108 PROTEIN_KINASE_ST, 2 hits

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiKS6A5_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O75582
Secondary accession number(s): B7Z2Y5, O95316, Q96AF7
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: November 1, 1998
Last modified: July 3, 2019
This is version 194 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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