Reviewed, UniProtKB/Swiss-Prot Q60855 (RIPK1_MOUSE)

Names and origin

Protein names

Recommended name:
    Receptor-interacting serine/threonine-protein kinase 1
    EC=2.7.11.1
Alternative name(s):
    Serine/threonine-protein kinase RIP
    Cell death protein RIP
    Receptor-interacting protein

Gene names

Name:	Ripk1
Synonyms:	Rinp, Rip

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	656 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the transduction of TNF signaling. TNF stimulation induces binding of RIPK1-TRADD-TRAF2-TRAF5 complex to TNFR1. TRAF proteins then catalyze the 'Lys-63'-linked polyubiquitination of RIPK1, inducing RIPK1 association with the IKK complex, which is subsequently activated, leading ultimately to the activation of NF-kappa-B. The inflammatory response is kept transient by the action of the NF-kappa-B target gene product TNFAIP3. TNFAIP3 is recruited to RIPK1 within a complex comprising also RNF11, ITCH and TAX1BP1. TNFAIP3 deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteosomal degradation and consequently to the termination of the TNF- or LPS-mediated activation of NF-kappa-B By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Binds to the death domain of TNFRSF6 and TRADD. Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RIPK3, UBCE7IP1, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5 By similarity.
Subcellular location	Cytoplasm.
Tissue specificity	Found at low levels in all tissues.
Induction	In concanavalin A-treated splenocytes.
Post-translational modification	Proteolytically cleaved by caspase-8 during TNF-induced apoptosis. Cleavage abolishes NF-kappa-B activation and enhances pro-apototic signaling through the TRADD-FADD interaction By similarity. Autophosphorylated on serine and threonine residues By similarity. Undergoes 'Lys-63'-polyubiquitination catalyzed by TRAF2 after TNF stimulation. Down-regulated by 'Lys-63'-deubiquitination and 'Lys-48'-ubiquitination, both reactions being catalyzed by TNFAIP3. 'Lys-48'-ubiquitination leads to proteasomal degradation By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 1 death domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Map3k8	Q07174	1	EBI-529119,EBI-309771
Ripk3	Q9QZL0	2	EBI-529119,EBI-2367423

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 656	656	Receptor-interacting serine/threonine-protein kinase 1		PRO_0000086607
Regions
	Domain	17 – 290	274	Protein kinase
	Domain	568 – 654	87	Death
	Nucleotide binding	23 – 31	9	ATP By similarity
	Region	291 – 567	277	Interaction with SQSTM1
Sites
	Active site	138	1	Proton acceptor By similarity
	Binding site	46	1	ATP By similarity
Amino acid modifications
	Modified residue	313	1	Phosphoserine Ref.4
	Modified residue	321	1	Phosphoserine By similarity
	Modified residue	383	1	Phosphotyrosine By similarity
Natural variations
	Natural variant	473	1	T → I
Experimental info
	Sequence conflict	66	1	M → K in BAC27194. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q60855-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: ABB350B523879933	FASTA	656	74,854
	10 20 30 40 50 60 MQPDMSLDNI KMASSDLLEK TDLDSGGFGK VSLCYHRSHG FVILKKVYTG PNRAEYNEVL 70 80 90 100 110 120 LEEGKMMHRL RHSRVVKLLG IIIEEGNYSL VMEYMEKGNL MHVLKTQIDV PLSLKGRIIV 130 140 150 160 170 180 EAIEGMCYLH DKGVIHKDLK PENILVDRDF HIKIADLGVA SFKTWSKLTK EKDNKQKEVS 190 200 210 220 230 240 STTKKNNGGT LYYMAPEHLN DINAKPTEKS DVYSFGIVLW AIFAKKEPYE NVICTEQFVI 250 260 270 280 290 300 CIKSGNRPNV EEILEYCPRE IISLMERCWQ AIPEDRPTFL GIEEEFRPFY LSHFEEYVEE 310 320 330 340 350 360 DVASLKKEYP DQSPVLQRMF SLQHDCVPLP PSRSNSEQPG SLHSSQGLQM GPVEESWFSS 370 380 390 400 410 420 SPEYPQDEND RSVQAKLQEE ASYHAFGIFA EKQTKPQPRQ NEAYNREEER KRRVSHDPFA 430 440 450 460 470 480 QQRARENIKS AGARGHSDPS TTSRGIAVQQ LSWPATQTVW NNGLYNQHGF GTTGTGVWYP 490 500 510 520 530 540 PNLSQMYSTY KTPVPETNIP GSTPTMPYFS GPVADDLIKY TIFNSSGIQI GNHNYMDVGL 550 560 570 580 590 600 NSQPPNNTCK EESTSRHQAI FDNTTSLTDE HLNPIRENLG RQWKNCARKL GFTESQIDEI 610 620 630 640 650 DHDYERDGLK EKVYQMLQKW LMREGTKGAT VGKLAQALHQ CCRIDLLNHL IRASQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death." Stanger B.Z., Leder P., Lee T.-H., Kim E., Seed B. Cell 81:513-523(1995) [PubMed: 7538908] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 X CBA. Tissue: Thymus.
[2]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Spleen and Thymus.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain and Liver.
[4]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed: 19144319] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-313, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U25995 mRNA. Translation: AAB60487.1. AK030959 mRNA. Translation: BAC27194.1. AK156803 mRNA. Translation: BAE33860.1. BC050905 mRNA. Translation: AAH50905.2. BC054542 mRNA. Translation: AAH54542.1. BC058162 mRNA. Translation: AAH58162.1.
IPI	IPI00121472.
PIR	I49299.
RefSeq	NP_033094.3.
UniGene	Mm.374799
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-34962N.
IntAct	Q60855. 4 interactions.
STRING	Q60855.
PTM databases
PhosphoSite	Q60855.
Proteomic databases
PRIDE	Q60855.
Genome annotation databases
Ensembl	ENSMUST00000021844; ENSMUSP00000021844; ENSMUSG00000021408; Mus musculus. [Genome view]
GeneID	19766.
KEGG	mmu:19766.
UCSC	uc007qax.1. mouse.
Organism-specific databases
CTD	19766.
MGI	MGI:108212. Ripk1.
Phylogenomic databases
HOGENOM	HBG445889.
HOVERGEN	Q60855.
InParanoid	Q60855.
OMA	SHDPFAQ.
OrthoDB	EOG9VDSJ8.
Enzyme and pathway databases
BRENDA	2.7.10.2. 244. 2.7.11.1. 244.
Gene expression databases
ArrayExpress	Q60855.
Bgee	Q60855.
Genevestigator	Q60855.
GermOnline	ENSMUSG00000021408. Mus musculus.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
Pfam	PF00531. Death. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00005. DEATH. 1 hit. [Graphical view]
PROSITE	PS50017. DEATH_DOMAIN. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	297220.
SOURCE	Search...

Entry information

Entry name

RIPK1_MOUSE

Accession

Primary (citable) accession number: Q60855
Secondary accession number(s): Q3U0J3, Q8CD90

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	December 15, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)