Reviewed, UniProtKB/Swiss-Prot P57078 (RIPK4_HUMAN)

Names and origin

Protein names

Recommended name:
    Receptor-interacting serine/threonine-protein kinase 4
    EC=2.7.11.1
Alternative name(s):
    Ankyrin repeat domain-containing protein 3
    PKC-delta-interacting protein kinase

Gene names

Name:	RIPK4
Synonyms:	ANKRD3, DIK

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

General annotation (Comments)

Function	Plays a role in NF-kappa B activation.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with PRKCB By similarity. Interacts with TRAF1, TRAF2, TRAF3 and TRAF5.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane proteinBy similarity.
Post-translational modification	May be phosphorylated by MAP3K2 and MAP3K3 By similarity. Proteolytically cleaved by during Fas-induced apoptosis. Cleavage at Asp-388 and Asp-426.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 10 ANK repeats. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P57078-1)

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: P57078-2)

The sequence of this isoform differs from the canonical sequence as follows:
     278-325: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 832	832	Receptor-interacting serine/threonine-protein kinase 4		PRO_0000086613
Regions
	Domain	22 – 286	265	Protein kinase
	Repeat	485 – 514	30	ANK 1
	Repeat	518 – 547	30	ANK 2
	Repeat	551 – 580	30	ANK 3
	Repeat	584 – 613	30	ANK 4
	Repeat	617 – 647	31	ANK 5
	Repeat	651 – 680	30	ANK 6
	Repeat	684 – 713	30	ANK 7
	Repeat	717 – 746	30	ANK 8
	Repeat	750 – 780	31	ANK 9
	Repeat	782 – 811	30	ANK 10
	Nucleotide binding	28 – 36	9	ATP By similarity
Sites
	Active site	143	1	Proton acceptor By similarity
	Binding site	51	1	ATP By similarity
	Site	388 – 389	2	Cleavage
	Site	426 – 427	2	Cleavage
Natural variations
	Alternative sequence	278 – 325	48	Missing in isoform 2.		VSP_004862
	Natural variant	12	1	A → G: dbSNP rs6586239.		VAR_030160
	Natural variant	177	1	S → N: dbSNP rs12482626.		VAR_030161
	Natural variant	462	1	I → N		VAR_041050
	Natural variant	463	1	V → M		VAR_041051
	Natural variant	562	1	N → Y		VAR_041052
	Natural variant	669	1	R → H		VAR_041053
	Natural variant	749	1	P → S		VAR_041054
Experimental info
	Sequence conflict	714	1	M → V in BAB56136. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2000. Version 1. Checksum: 5D8FFFD5F04F7ECB	FASTA	832	91,611
	10 20 30 40 50 60 MEGDGGTPWA LALLRTFDAG EFTGWEKVGS GGFGQVYKVR HVHWKTWLAI KCSPSLHVDD 70 80 90 100 110 120 RERMELLEEA KKMEMAKFRY ILPVYGICRE PVGLVMEYME TGSLEKLLAS EPLPWDLRFR 130 140 150 160 170 180 IIHETAVGMN FLHCMAPPLL HLDLKPANIL LDAHYHVKIS DFGLAKCNGL SHSHDLSMDG 190 200 210 220 230 240 LFGTIAYLPP ERIREKSRLF DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMVKVVKGH 250 260 270 280 290 300 RPELPPVCRA RPRACSHLIR LMQRCWQGDP RVRPTFQGNG LNGELIRQVL AALLPVTGRW 310 320 330 340 350 360 RSPGEGFRLE SEVIIRVTCP LSSPQEITSE TEDLCEKPDD EVKETAHDLD VKSPPEPRSE 370 380 390 400 410 420 VVPARLKRAS APTFDNDYSL SELLSQLDSG VSQAVEGPEE LSRSSSESKL PSSGSGKRLS 430 440 450 460 470 480 GVSSVDSAFS SRGSLSLSFE REPSTSDLGT TDVQKKKLVD AIVSGDTSKL MKILQPQDVD 490 500 510 520 530 540 LALDSGASLL HLAVEAGQEE CAKWLLLNNA NPNLSNRRGS TPLHMAVERR VRGVVELLLA 550 560 570 580 590 600 RKISVNAKDE DQWTALHFAA QNGDESSTRL LLEKNASVNE VDFEGRTPMH VACQHGQENI 610 620 630 640 650 660 VRILLRRGVD VSLQGKDAWL PLHYAAWQGH LPIVKLLAKQ PGVSVNAQTL DGRTPLHLAA 670 680 690 700 710 720 QRGHYRVARI LIDLCSDVNV CSLLAQTPLH VAAETGHTST ARLLLHRGAG KEAMTSDGYT 730 740 750 760 770 780 ALHLAARNGH LATVKLLVEE KADVLARGPL NQTALHLAAA HGHSEVVEEL VSADVIDLFD 790 800 810 820 830 EQGLSALHLA AQGRHAQTVE TLLRHGAHIN LQSLKFQGGH GPAATLLRRS KT
	Isoform 2 [UniParc]. Checksum: EEE7DBD53135AA91		784	86,441
	10 20 30 40 50 60 MEGDGGTPWA LALLRTFDAG EFTGWEKVGS GGFGQVYKVR HVHWKTWLAI KCSPSLHVDD 70 80 90 100 110 120 RERMELLEEA KKMEMAKFRY ILPVYGICRE PVGLVMEYME TGSLEKLLAS EPLPWDLRFR 130 140 150 160 170 180 IIHETAVGMN FLHCMAPPLL HLDLKPANIL LDAHYHVKIS DFGLAKCNGL SHSHDLSMDG 190 200 210 220 230 240 LFGTIAYLPP ERIREKSRLF DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMVKVVKGH 250 260 270 280 290 300 RPELPPVCRA RPRACSHLIR LMQRCWQGDP RVRPTFQEIT SETEDLCEKP DDEVKETAHD 310 320 330 340 350 360 LDVKSPPEPR SEVVPARLKR ASAPTFDNDY SLSELLSQLD SGVSQAVEGP EELSRSSSES 370 380 390 400 410 420 KLPSSGSGKR LSGVSSVDSA FSSRGSLSLS FEREPSTSDL GTTDVQKKKL VDAIVSGDTS 430 440 450 460 470 480 KLMKILQPQD VDLALDSGAS LLHLAVEAGQ EECAKWLLLN NANPNLSNRR GSTPLHMAVE 490 500 510 520 530 540 RRVRGVVELL LARKISVNAK DEDQWTALHF AAQNGDESST RLLLEKNASV NEVDFEGRTP 550 560 570 580 590 600 MHVACQHGQE NIVRILLRRG VDVSLQGKDA WLPLHYAAWQ GHLPIVKLLA KQPGVSVNAQ 610 620 630 640 650 660 TLDGRTPLHL AAQRGHYRVA RILIDLCSDV NVCSLLAQTP LHVAAETGHT STARLLLHRG 670 680 690 700 710 720 AGKEAMTSDG YTALHLAARN GHLATVKLLV EEKADVLARG PLNQTALHLA AAHGHSEVVE 730 740 750 760 770 780 ELVSADVIDL FDEQGLSALH LAAQGRHAQT VETLLRHGAH INLQSLKFQG GHGPAATLLR RSKT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Shimizu N., Kudoh J., Shibuya K. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Fetal kidney and Fetal lung.
[2]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-kappa B and is processed during apoptosis." Meylan E., Martinon F., Thome M., Gschwendt M., Tschopp J. EMBO Rep. 3:1201-1208(2002) [PubMed: 12446564] [Abstract] Cited for: CLEAVAGE AT ASP-388 AND ASP-426, INTERACTION WITH TRAF1; TRAF2; TRAF3 AND TRAF5, FUNCTION.
[4]	"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] ASN-462; MET-463; TYR-562; HIS-669 AND SER-749.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB047783 mRNA. Translation: BAB56136.1. AP001743 Genomic DNA. Translation: BAA95526.1.
UniGene	Hs.517310
3D structure databases
HSSP	HSSP built from PDB template 1OY3 based on UniProtKB Q60778.
ModBase	Search...
PTM databases
PhosphoSite	P57078.
Genome annotation databases
Ensembl	ENSG00000183421. Homo sapiens. [Contig view]
Organism-specific databases
HGNC	HGNC:496. RIPK4.
MIM	605706. gene.
PharmGKB	PA24805.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P57078.
HOVERGEN	P57078.
Gene expression databases
ArrayExpress	P57078.
CleanEx	HS_RIPK4.
GermOnline	ENSG00000183421. Homo sapiens.
Family and domain databases
InterPro	IPR002110. ANK. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00023. Ank. 10 hits. PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00248. ANK. 10 hits. [Graphical view]
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 9 hits. 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

RIPK4_HUMAN

Accession

Primary (citable) accession number: P57078
Secondary accession number(s): Q96KH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	November 25, 2008
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)