Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P57078

- RIPK4_HUMAN

UniProt

P57078 - RIPK4_HUMAN

Protein

Receptor-interacting serine/threonine-protein kinase 4

Gene

RIPK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 1 (01 Dec 2000)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei51 – 511ATPPROSITE-ProRule annotation
    Active sitei143 – 1431Proton acceptorPROSITE-ProRule annotation
    Sitei388 – 3892Cleavage
    Sitei426 – 4272Cleavage

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi28 – 369ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. morphogenesis of an epithelium Source: UniProtKB
    2. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Receptor, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiP57078.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:RIPK4
    Synonyms:ANKRD3, DIK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 21

    Organism-specific databases

    HGNCiHGNC:496. RIPK4.

    Subcellular locationi

    Cytoplasm. Membrane By similarity; Peripheral membrane protein By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. membrane Source: UniProtKB-SubCell
    3. nucleus Source: HPA

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti81 – 811I → N in PPS-L. 1 Publication
    VAR_067331
    Natural varianti121 – 1211I → N in PPS-L; loss of function. 1 Publication
    VAR_067332
    Natural varianti184 – 1841T → I in PPS-L; loss of function. 1 Publication
    VAR_067333

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi263650. phenotype.
    Orphaneti1234. Bartsocas-Papas syndrome.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 832832Receptor-interacting serine/threonine-protein kinase 4PRO_0000086613Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki51 – 51Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki145 – 145Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

    Post-translational modificationi

    May be phosphorylated by MAP3K2 and MAP3K3.By similarity
    Proteolytically cleaved by during Fas-induced apoptosis. Cleavage at Asp-388 and Asp-426.1 Publication
    Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.1 Publication

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP57078.
    PaxDbiP57078.
    PRIDEiP57078.

    PTM databases

    PhosphoSiteiP57078.

    Expressioni

    Gene expression databases

    ArrayExpressiP57078.
    BgeeiP57078.
    CleanExiHS_RIPK4.
    GenevestigatoriP57078.

    Organism-specific databases

    HPAiHPA021158.

    Interactioni

    Subunit structurei

    Interacts with PRKCB By similarity. Interacts with TRAF1, TRAF2, TRAF3 and TRAF5. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    BIRC2Q134903EBI-4422308,EBI-514538
    BIRC3Q134893EBI-4422308,EBI-517709
    XIAPP981702EBI-4422308,EBI-517127

    Protein-protein interaction databases

    IntActiP57078. 4 interactions.
    MINTiMINT-142997.
    STRINGi9606.ENSP00000332454.

    Structurei

    3D structure databases

    ProteinModelPortaliP57078.
    SMRiP57078. Positions 17-359, 394-810.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini22 – 286265Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Repeati485 – 51430ANK 1Add
    BLAST
    Repeati518 – 54730ANK 2Add
    BLAST
    Repeati551 – 58030ANK 3Add
    BLAST
    Repeati584 – 61330ANK 4Add
    BLAST
    Repeati617 – 64731ANK 5Add
    BLAST
    Repeati651 – 68030ANK 6Add
    BLAST
    Repeati684 – 71330ANK 7Add
    BLAST
    Repeati717 – 74630ANK 8Add
    BLAST
    Repeati750 – 78031ANK 9Add
    BLAST
    Repeati782 – 81130ANK 10Add
    BLAST

    Sequence similaritiesi

    Contains 10 ANK repeats.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    ANK repeat, Repeat

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000294086.
    HOVERGENiHBG061582.
    InParanoidiP57078.
    OMAiVCRARPR.
    OrthoDBiEOG78H3SS.
    PhylomeDBiP57078.
    TreeFamiTF106506.

    Family and domain databases

    Gene3Di1.25.40.20. 4 hits.
    InterProiIPR002110. 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]
    PfamiPF12796. Ank_2. 4 hits.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    PRINTSiPR01415. ANKYRIN.
    SMARTiSM00248. ANK. 10 hits.
    [Graphical view]
    SUPFAMiSSF48403. SSF48403. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50297. 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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P57078-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MEGDGGTPWA LALLRTFDAG EFTGWEKVGS GGFGQVYKVR HVHWKTWLAI    50
    KCSPSLHVDD RERMELLEEA KKMEMAKFRY ILPVYGICRE PVGLVMEYME 100
    TGSLEKLLAS EPLPWDLRFR IIHETAVGMN FLHCMAPPLL HLDLKPANIL 150
    LDAHYHVKIS DFGLAKCNGL SHSHDLSMDG LFGTIAYLPP ERIREKSRLF 200
    DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMVKVVKGH RPELPPVCRA 250
    RPRACSHLIR LMQRCWQGDP RVRPTFQGNG LNGELIRQVL AALLPVTGRW 300
    RSPGEGFRLE SEVIIRVTCP LSSPQEITSE TEDLCEKPDD EVKETAHDLD 350
    VKSPPEPRSE VVPARLKRAS APTFDNDYSL SELLSQLDSG VSQAVEGPEE 400
    LSRSSSESKL PSSGSGKRLS GVSSVDSAFS SRGSLSLSFE REPSTSDLGT 450
    TDVQKKKLVD AIVSGDTSKL MKILQPQDVD LALDSGASLL HLAVEAGQEE 500
    CAKWLLLNNA NPNLSNRRGS TPLHMAVERR VRGVVELLLA RKISVNAKDE 550
    DQWTALHFAA QNGDESSTRL LLEKNASVNE VDFEGRTPMH VACQHGQENI 600
    VRILLRRGVD VSLQGKDAWL PLHYAAWQGH LPIVKLLAKQ PGVSVNAQTL 650
    DGRTPLHLAA QRGHYRVARI LIDLCSDVNV CSLLAQTPLH VAAETGHTST 700
    ARLLLHRGAG KEAMTSDGYT ALHLAARNGH LATVKLLVEE KADVLARGPL 750
    NQTALHLAAA HGHSEVVEEL VSADVIDLFD EQGLSALHLA AQGRHAQTVE 800
    TLLRHGAHIN LQSLKFQGGH GPAATLLRRS KT 832
    Length:832
    Mass (Da):91,611
    Last modified:December 1, 2000 - v1
    Checksum:i5D8FFFD5F04F7ECB
    GO
    Isoform 2 (identifier: P57078-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:784
    Mass (Da):86,441
    Checksum:iEEE7DBD53135AA91
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti714 – 7141M → V in BAB56136. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121A → G.
    Corresponds to variant rs6586239 [ dbSNP | Ensembl ].
    VAR_030160
    Natural varianti81 – 811I → N in PPS-L. 1 Publication
    VAR_067331
    Natural varianti121 – 1211I → N in PPS-L; loss of function. 1 Publication
    VAR_067332
    Natural varianti177 – 1771S → N.
    Corresponds to variant rs12482626 [ dbSNP | Ensembl ].
    VAR_030161
    Natural varianti184 – 1841T → I in PPS-L; loss of function. 1 Publication
    VAR_067333
    Natural varianti462 – 4621I → N.1 Publication
    VAR_041050
    Natural varianti463 – 4631V → M.1 Publication
    Corresponds to variant rs55645753 [ dbSNP | Ensembl ].
    VAR_041051
    Natural varianti562 – 5621N → Y.1 Publication
    Corresponds to variant rs55829311 [ dbSNP | Ensembl ].
    VAR_041052
    Natural varianti669 – 6691R → H.1 Publication
    VAR_041053
    Natural varianti749 – 7491P → S.1 Publication
    Corresponds to variant rs35537517 [ dbSNP | Ensembl ].
    VAR_041054

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei278 – 32548Missing in isoform 2. 1 PublicationVSP_004862Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB047783 mRNA. Translation: BAB56136.1.
    AP001743 Genomic DNA. Translation: BAA95526.1.
    CCDSiCCDS13675.1. [P57078-2]
    UniGeneiHs.517310.

    Genome annotation databases

    EnsembliENST00000332512; ENSP00000332454; ENSG00000183421. [P57078-2]
    ENST00000352483; ENSP00000330161; ENSG00000183421. [P57078-1]
    UCSCiuc002yzn.1. human. [P57078-2]

    Polymorphism databases

    DMDMi10719883.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB047783 mRNA. Translation: BAB56136.1 .
    AP001743 Genomic DNA. Translation: BAA95526.1 .
    CCDSi CCDS13675.1. [P57078-2 ]
    UniGenei Hs.517310.

    3D structure databases

    ProteinModelPortali P57078.
    SMRi P57078. Positions 17-359, 394-810.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P57078. 4 interactions.
    MINTi MINT-142997.
    STRINGi 9606.ENSP00000332454.

    Chemistry

    BindingDBi P57078.
    ChEMBLi CHEMBL6083.
    GuidetoPHARMACOLOGYi 2192.

    PTM databases

    PhosphoSitei P57078.

    Polymorphism databases

    DMDMi 10719883.

    Proteomic databases

    MaxQBi P57078.
    PaxDbi P57078.
    PRIDEi P57078.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000332512 ; ENSP00000332454 ; ENSG00000183421 . [P57078-2 ]
    ENST00000352483 ; ENSP00000330161 ; ENSG00000183421 . [P57078-1 ]
    UCSCi uc002yzn.1. human. [P57078-2 ]

    Organism-specific databases

    GeneCardsi GC21M043159.
    HGNCi HGNC:496. RIPK4.
    HPAi HPA021158.
    MIMi 263650. phenotype.
    605706. gene.
    neXtProti NX_P57078.
    Orphaneti 1234. Bartsocas-Papas syndrome.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000294086.
    HOVERGENi HBG061582.
    InParanoidi P57078.
    OMAi VCRARPR.
    OrthoDBi EOG78H3SS.
    PhylomeDBi P57078.
    TreeFami TF106506.

    Enzyme and pathway databases

    SignaLinki P57078.

    Miscellaneous databases

    ChiTaRSi RIPK4. human.
    PROi P57078.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P57078.
    Bgeei P57078.
    CleanExi HS_RIPK4.
    Genevestigatori P57078.

    Family and domain databases

    Gene3Di 1.25.40.20. 4 hits.
    InterProi IPR002110. 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 ]
    Pfami PF12796. Ank_2. 4 hits.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PRINTSi PR01415. ANKYRIN.
    SMARTi SM00248. ANK. 10 hits.
    [Graphical view ]
    SUPFAMi SSF48403. SSF48403. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi 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 ]
    ProtoNeti Search...

    Publicationsi

    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] [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. 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.
      , 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. Cited for: VARIANTS PPS-L ASN-121 AND ILE-184, CHARACTERIZATION OF VARIANTS PPS-L ASN-121 AND ILE-184.

    Entry informationi

    Entry nameiRIPK4_HUMAN
    AccessioniPrimary (citable) accession number: P57078
    Secondary accession number(s): Q96KH0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: December 1, 2000
    Last modified: October 1, 2014
    This is version 131 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 21
      Human chromosome 21: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3