Receptor-interacting serine/threonine-protein kinase 2

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Q3SZJ2 (RIPK2_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 71. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Receptor-interacting serine/threonine-protein kinase 2
EC=2.7.11.1

Alternative name(s):
Tyrosine-protein kinase RIPK2
EC=2.7.10.2

Gene names

Name:

RIPK2

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	540 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is release from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Binds to CFLAR/CLARP and CASP1 via their CARD domains. Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6. May be a component of both the TNFRSF1A and TNRFSF5/CD40 receptor complex. Interacts with NOD1 and NOD2. Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway. Interacts with IKBKG/NEMO. The polyubiquitinated protein interacts with MAP3K7/TAK1. Interacts with XIAP/BIRC4. Interacts with NLRP10 By similarity.
Subcellular location	Cytoplasm Probable.
Domain	Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins By similarity.
Post-translational modification	Autophosphorylated. Autophosphorylation at Tyr-472 is necessary for effective NOD2 signaling. Ubiquitinated on Lys-209; undergoes 'Lys-63'-linked polyubiquitination catalyzed by ITCH. Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 1 CARD domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Adaptive immunity Apoptosis Immunity Innate immunity
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: UniProtKB T cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB adaptive immune response Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 540

540

Receptor-interacting serine/threonine-protein kinase 2

PRO_0000245586

Regions

Domain

18 – 294

277

Protein kinase

Domain

432 – 524

CARD

Nucleotide binding

24 – 32

ATP By similarity

Sites

Active site

146

Proton acceptor

Binding site

ATP By similarity

Amino acid modifications

Modified residue

168

Phosphoserine By similarity

Modified residue

176

Phosphoserine; by autocatalysis By similarity

Modified residue

363

Phosphoserine By similarity

Modified residue

391

Phosphoserine By similarity

Modified residue

472

Phosphotyrosine; by autocatalysis By similarity

Modified residue

525

Phosphoserine By similarity

Modified residue

527

Phosphoserine By similarity

Modified residue

529

Phosphoserine By similarity

Modified residue

537

Phosphoserine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q3SZJ2 [UniParc].

Last modified October 11, 2005. Version 1.
Checksum: 2F54BD72A747970F
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FASTA

540

61,106

        10         20         30         40         50         60 
MSAEPVCSAL PAIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH IHSPLLDSER 

        70         80         90        100        110        120 
NDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK IEYPDVPWPL 

       130        140        150        160        170        180 
RFRILHEIAL GVNYLHNMNP PLLHHDLKTQ NILLDNEFHV KIADFGLSKW RMMSLSQSRS 

       190        200        210        220        230        240 
SKSAPEGGTI VYMPPENYEP GQKARASVKH DIYSYAIIIW EVLSRKQPFE DVTNPLQIMY 

       250        260        270        280        290        300 
SVSQGHRPDT NEESLPFDIP HRALMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI 

       310        320        330        340        350        360 
TFLEAVIQLK KTKLQNASRT VHLSDKKKRE LSPNIPVNSG PREESCGSSQ LHKTSGSPGT 

       370        380        390        400        410        420 
SRSLSAPQDK DFLSAKTQDF SALHQCSVNH SRNSDFCVDC QVAFCDHRTA PCSLAIVNPL 

       430        440        450        460        470        480 
SAEGNSGRFQ PGIAQQWIQS KREDIVSQMT EACLNQSLDA LLSRDLIMKE DYELISTKPT 

       490        500        510        520        530        540 
RTSKVRQLLD TTDIQGEEFA RVIVQKLKDN KQMGLQPYPE ILVLSQSPSL NFFHNKSHKK

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References

[1]	NIH - Mammalian Gene Collection (MGC) project Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Crossbred X Angus. Tissue: Ileum.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC102829 mRNA. Translation: AAI02830.1.
IPI	IPI00713042.
RefSeq	NP_001029782.1. NM_001034610.2.
UniGene	Bt.34596.
3D structure databases
ProteinModelPortal	Q3SZJ2.
ModBase	Search...
Protein-protein interaction databases
STRING	9913.ENSBTAP00000020312.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000020312; ENSBTAP00000020312; ENSBTAG00000015271.
GeneID	534407.
KEGG	bta:534407.
Organism-specific databases
CTD	8767.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074536.
HOGENOM	HOG000136856.
HOVERGEN	HBG054242.
InParanoid	Q3SZJ2.
KO	K08846.
OrthoDB	EOG4VQ9NZ.
Gene expression databases
ArrayExpress	Q3SZJ2.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR001315. CARD. IPR011029. DEATH-like_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017322. Rcpt-int_Ser/Thr_kinase-2. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00619. CARD. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF037921. STPK_RIP2. 1 hit.
SMART	SM00114. CARD. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS50209. CARD. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20876393.

Entry information

Entry name

RIPK2_BOVIN

Accession

Primary (citable) accession number: Q3SZJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2006
Last sequence update:	October 11, 2005
Last modified:	April 3, 2013
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents