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P57078 (RIPK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length832 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation. Ref.3 Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts with PRKCB By similarity. Interacts with TRAF1, TRAF2, TRAF3 and TRAF5. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Ref.3 Ref.4

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein By 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. Ref.3

Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.

Involvement in disease

Popliteal pterygium syndrome, lethal type (PPS-L) [MIM:263650]: An autosomal recessive disorder characterized by multiple popliteal pterygia leading to severe arthrogryposis, ankyloblepharon filiforme adnatum, filiform bands between the jaws, synostosis of the carpal/tarsal and phalangeal bones in the hands and feet, digital hypoplasia/aplasia, complete soft-tissue syndactyly, lack of nails, lack of scalp hair, eyebrows and eyelashes, blepharophimosis, cleft lip and/or palate, and hypoplastic external genitalia. Early lethality is common, although survival into childhood and beyond has been reported.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 10 ANK repeats.

Contains 1 protein kinase domain.

Binary interactions

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 832832Receptor-interacting serine/threonine-protein kinase 4
PRO_0000086613

Regions

Domain22 – 286265Protein kinase
Repeat485 – 51430ANK 1
Repeat518 – 54730ANK 2
Repeat551 – 58030ANK 3
Repeat584 – 61330ANK 4
Repeat617 – 64731ANK 5
Repeat651 – 68030ANK 6
Repeat684 – 71330ANK 7
Repeat717 – 74630ANK 8
Repeat750 – 78031ANK 9
Repeat782 – 81130ANK 10
Nucleotide binding28 – 369ATP By similarity

Sites

Active site1431Proton acceptor By similarity
Binding site511ATP By similarity
Site388 – 3892Cleavage
Site426 – 4272Cleavage

Amino acid modifications

Cross-link51Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.4
Cross-link145Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.4

Natural variations

Alternative sequence278 – 32548Missing in isoform 2.
VSP_004862
Natural variant121A → G.
Corresponds to variant rs6586239 [ dbSNP | Ensembl ].
VAR_030160
Natural variant811I → N in PPS-L. Ref.5
VAR_067331
Natural variant1211I → N in PPS-L; loss of function. Ref.7
VAR_067332
Natural variant1771S → N.
Corresponds to variant rs12482626 [ dbSNP | Ensembl ].
VAR_030161
Natural variant1841T → I in PPS-L; loss of function. Ref.7
VAR_067333
Natural variant4621I → N. Ref.6
VAR_041050
Natural variant4631V → M. Ref.6
Corresponds to variant rs55645753 [ dbSNP | Ensembl ].
VAR_041051
Natural variant5621N → Y. Ref.6
Corresponds to variant rs55829311 [ dbSNP | Ensembl ].
VAR_041052
Natural variant6691R → H. Ref.6
VAR_041053
Natural variant7491P → S. Ref.6
Corresponds to variant rs35537517 [ dbSNP | Ensembl ].
VAR_041054

Experimental info

Sequence conflict7141M → V in BAB56136. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2000. Version 1.
Checksum: 5D8FFFD5F04F7ECB

FASTA83291,611
        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 

« Hide

Isoform 2 [UniParc].

Checksum: EEE7DBD53135AA91
Show »

FASTA78486,441

References

« Hide '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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: CLEAVAGE AT ASP-388 AND ASP-426, INTERACTION WITH TRAF1; TRAF2; TRAF3 AND TRAF5, FUNCTION.
[4]"cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."
Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J., Gevaert K., Declercq W., Vandenabeele P.
PLoS ONE 6:E22356-E22356(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-51 AND LYS-145, UBIQUITINATION BY BIRC2/C-IAP1 AND BIRC3/C-IAP2, INTERACTION WITH BIRC2/C-IAP1; BIRC3/C-IAP2 AND XIAP/BIRC4.
[5]"Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus."
Mitchell K., O'Sullivan J., Missero C., Blair E., Richardson R., Anderson B., Antonini D., Murray J.C., Shanske A.L., Schutte B.C., Romano R.A., Sinha S., Bhaskar S.S., Black G.C., Dixon J., Dixon M.J.
Am. J. Hum. Genet. 90:69-75(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANT PPS-L ASN-81.
[6]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-462; MET-463; TYR-562; HIS-669 AND SER-749.
[7]"Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome."
Kalay E., Sezgin O., Chellappa V., Mutlu M., Morsy H., Kayserili H., Kreiger E., Cansu A., Toraman B., Abdalla E.M., Aslan Y., Pillai S., Akarsu N.A.
Am. J. Hum. Genet. 90:76-85(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPS-L ASN-121 AND ILE-184, CHARACTERIZATION OF VARIANTS PPS-L ASN-121 AND ILE-184.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB047783 mRNA. Translation: BAB56136.1.
AP001743 Genomic DNA. Translation: BAA95526.1.
CCDSCCDS13675.1. [P57078-2]
UniGeneHs.517310.

3D structure databases

ProteinModelPortalP57078.
SMRP57078. Positions 17-359, 394-810.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP57078. 4 interactions.
MINTMINT-142997.
STRING9606.ENSP00000332454.

Chemistry

BindingDBP57078.
ChEMBLCHEMBL6083.
GuidetoPHARMACOLOGY2192.

PTM databases

PhosphoSiteP57078.

Polymorphism databases

DMDM10719883.

Proteomic databases

MaxQBP57078.
PaxDbP57078.
PRIDEP57078.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332512; ENSP00000332454; ENSG00000183421. [P57078-2]
ENST00000352483; ENSP00000330161; ENSG00000183421. [P57078-1]
UCSCuc002yzn.1. human. [P57078-2]

Organism-specific databases

GeneCardsGC21M043159.
HGNCHGNC:496. RIPK4.
HPAHPA021158.
MIM263650. phenotype.
605706. gene.
neXtProtNX_P57078.
Orphanet1234. Bartsocas-Papas syndrome.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000294086.
HOVERGENHBG061582.
InParanoidP57078.
OMAVCRARPR.
OrthoDBEOG78H3SS.
PhylomeDBP57078.
TreeFamTF106506.

Enzyme and pathway databases

SignaLinkP57078.

Gene expression databases

ArrayExpressP57078.
BgeeP57078.
CleanExHS_RIPK4.
GenevestigatorP57078.

Family and domain databases

Gene3D1.25.40.20. 4 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF12796. Ank_2. 4 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 10 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50297. 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]
ProtoNetSearch...

Other

ChiTaRSRIPK4. human.
PROP57078.
SOURCESearch...

Entry information

Entry nameRIPK4_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM