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P57078

- RIPK4_HUMAN

UniProt

P57078 - RIPK4_HUMAN

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Protein
Receptor-interacting serine/threonine-protein kinase 4
Gene
RIPK4, ANKRD3, DIK
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 – 511ATP By similarity
Active sitei143 – 1431Proton acceptor By similarity
Sitei388 – 3892Cleavage
Sitei426 – 4272Cleavage

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi28 – 369ATP By similarity

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
Complete GO annotation...

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

GO - Cellular componenti

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

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.2 Publications
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 4
PRO_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.

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/BIRC4.2 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.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Contains 10 ANK repeats.

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

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.
VSP_004862Add
BLAST

Sequence conflict

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

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 130 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

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