Reviewed, UniProtKB/Swiss-Prot Q9Y572 (RIPK3_HUMAN)

Names and origin

Protein names

Recommended name:
    Receptor-interacting serine/threonine-protein kinase 3
    EC=2.7.11.1
Alternative name(s):
    RIP-like protein kinase 3
    Receptor-interacting protein 3
      Short name=RIP-3

Gene names

Name:	RIPK3
Synonyms:	RIP3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	518 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Promotes apoptosis.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Binds TRAF2 and RIPK1 and is recruited to the TNFR-1 signaling complex.
Subcellular location	Cytoplasm Probable.
Tissue specificity	Highly expressed in the pancreas. Detected at lower levels in heart, placenta, lung and kidney. Isoform 3 is significantly increased in colon and lung cancers. Ref.3
Post-translational modification	Autophosphorylated By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis by extracellular signals Ref.1 Traceable author statement. Source: ProtInc protein amino acid phosphorylation 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 transcription coactivator activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y572-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y572-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     220-518: VELPTEPSLV...PQGWYNHSGK → CQPNHHSCTKQCATGRTGLHWLSCPKPGLRLPA

Isoform 3 (identifier: Q9Y572-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     222-518: LPTEPSLVYE...PQGWYNHSGK → CKTLGGFWDP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 518	518	Receptor-interacting serine/threonine-protein kinase 3		PRO_0000086610
Regions
	Domain	21 – 287	267	Protein kinase
	Nucleotide binding	27 – 35	9	ATP By similarity
Sites
	Active site	142	1	Proton acceptor By similarity
	Binding site	50	1	ATP
Natural variations
	Alternative sequence	220 – 518	299	VELPT…NHSGK → CQPNHHSCTKQCATGRTGLH WLSCPKPGLRLPA in isoform 2.		VSP_035106
	Alternative sequence	222 – 518	297	LPTEP…NHSGK → CKTLGGFWDP in isoform 3.		VSP_035107
	Natural variant	260	1	E → V: dbSNP rs7153640.		VAR_051664
	Natural variant	300	1	T → M: dbSNP rs34106261. Ref.7		VAR_041048
	Natural variant	492	1	P → Q: dbSNP rs3212254. Ref.7		VAR_041049
Experimental info
	Mutagenesis	50	1	K → A: Abolishes kinase activity. Ref.1 Ref.2
	Mutagenesis	50	1	K → D: Abolishes kinase activity. Ref.1 Ref.2
	Sequence conflict	30	1	G → D in AAD39005. Ref.1
	Sequence conflict	150	1	L → P in AAD39005. Ref.1
	Sequence conflict	309	1	R → K in AAD39005. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: BF755F8A0B1810A1	FASTA	518	56,887
	10 20 30 40 50 60 MSCVKLWPSG APAPLVSIEE LENQELVGKG GFGTVFRAQH RKWGYDVAVK IVNSKAISRE 70 80 90 100 110 120 VKAMASLDNE FVLRLEGVIE KVNWDQDPKP ALVTKFMENG SLSGLLQSQC PRPWPLLCRL 130 140 150 160 170 180 LKEVVLGMFY LHDQNPVLLH RDLKPSNVLL DPELHVKLAD FGLSTFQGGS QSGTGSGEPG 190 200 210 220 230 240 GTLGYLAPEL FVNVNRKAST ASDVYSFGIL MWAVLAGREV ELPTEPSLVY EAVCNRQNRP 250 260 270 280 290 300 SLAELPQAGP ETPGLEGLKE LMQLCWSSEP KDRPSFQECL PKTDEVFQMV ENNMNAAVST 310 320 330 340 350 360 VKDFLSQLRS SNRRFSIPES GQGGTEMDGF RRTIENQHSR NDVMVSEWLN KLNLEEPPSS 370 380 390 400 410 420 VPKKCPSLTK RSRAQEEQVP QAWTAGTSSD SMAQPPQTPE TSTFRNQMPS PTSTGTPSPG 430 440 450 460 470 480 PRGNQGAERQ GMNWSCRTPE PNPVTGRPLV NIYNCSGVQV GDNNYLTMQQ TTALPTWGLA 490 500 510 PSGKGRGLQH PPPVGSQEGP KDPEAWSRPQ GWYNHSGK
	Isoform 2 (Beta). Checksum: 20D7DFAB11AEECEF	FASTA	252	27,574
	10 20 30 40 50 60 MSCVKLWPSG APAPLVSIEE LENQELVGKG GFGTVFRAQH RKWGYDVAVK IVNSKAISRE 70 80 90 100 110 120 VKAMASLDNE FVLRLEGVIE KVNWDQDPKP ALVTKFMENG SLSGLLQSQC PRPWPLLCRL 130 140 150 160 170 180 LKEVVLGMFY LHDQNPVLLH RDLKPSNVLL DPELHVKLAD FGLSTFQGGS QSGTGSGEPG 190 200 210 220 230 240 GTLGYLAPEL FVNVNRKAST ASDVYSFGIL MWAVLAGREC QPNHHSCTKQ CATGRTGLHW 250 LSCPKPGLRL PA
	Isoform 3 (Gamma). Checksum: 8E6E045EC3B11DEF	FASTA	231	25,326
	10 20 30 40 50 60 MSCVKLWPSG APAPLVSIEE LENQELVGKG GFGTVFRAQH RKWGYDVAVK IVNSKAISRE 70 80 90 100 110 120 VKAMASLDNE FVLRLEGVIE KVNWDQDPKP ALVTKFMENG SLSGLLQSQC PRPWPLLCRL 130 140 150 160 170 180 LKEVVLGMFY LHDQNPVLLH RDLKPSNVLL DPELHVKLAD FGLSTFQGGS QSGTGSGEPG 190 200 210 220 230 GTLGYLAPEL FVNVNRKAST ASDVYSFGIL MWAVLAGREV ECKTLGGFWD P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB." Yu P.W., Huang B.C.B., Shen M., Quast J., Chan E., Xu X., Nolan G.P., Payan D.G., Luo Y. Curr. Biol. 9:539-542(1999) [PubMed: 10339433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-50. Tissue: Cervix carcinoma and Lymphocyte.
[2]	"RIP3, a novel apoptosis-inducing kinase." Sun X., Lee J., Navas T., Baldwin D.T., Stewart T.A., Dixit V.M. J. Biol. Chem. 274:16871-16875(1999) [PubMed: 10358032] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-50. Tissue: Aortic endothelium and Fetal brain.
[3]	"RIP3 beta and RIP3 gamma, two novel splice variants of receptor-interacting protein 3 (RIP3), downregulate RIP3-induced apoptosis." Yang Y., Hu W., Feng S., Ma J., Wu M. Biochem. Biophys. Res. Commun. 332:181-187(2005) [PubMed: 15896315] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Thalamus.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Blood.
[7]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-300 AND GLN-492.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF156884 mRNA. Translation: AAD39005.1. AY453693 mRNA. Translation: AAS16359.1. AY494982 mRNA. Translation: AAS75516.1. AY494983 mRNA. Translation: AAS75517.1. AK296140 mRNA. Translation: BAG58881.1. CH471078 Genomic DNA. Translation: EAW66021.1. BC062584 mRNA. Translation: AAH62584.1.
IPI	IPI00418712. IPI00847572. IPI00896383.
RefSeq	NP_006862.2.
UniGene	Hs.268551
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y572. 83 interactions.
Proteomic databases
PRIDE	Q9Y572.
Genome annotation databases
Ensembl	ENSG00000129465. Homo sapiens. [Contig view]
GeneID	11035.
KEGG	hsa:11035.
Organism-specific databases
GeneCards	GC14M023875.
HGNC	HGNC:10021. RIPK3.
MIM	605817. gene.
PharmGKB	PA34396.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9Y572.
HOVERGEN	Q9Y572.
OMA	Q9Y572. TRFMENG.
Enzyme and pathway databases
BRENDA	2.7.10.2. 247. 2.7.11.1. 247.
Gene expression databases
ArrayExpress	Q9Y572.
Bgee	Q9Y572.
CleanEx	HS_RIPK3.
GermOnline	ENSG00000129465. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

RIPK3_HUMAN

Accession

Primary (citable) accession number: Q9Y572
Secondary accession number(s): B4DJL9 , Q5J795, Q5J796, Q6P5Y1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	September 2, 2008
Last modified:	June 16, 2009
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)