Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Receptor-interacting serine/threonine-protein kinase 4

Gene

RIPK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei51ATPPROSITE-ProRule annotation1
Active sitei143Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi28 – 36ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • morphogenesis of an epithelium Source: UniProtKB
  • 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

BioCyciZFISH:HS11966-MONOMER.
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
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:496. RIPK4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Popliteal pterygium syndrome, lethal type (PPS-L)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:263650
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06733181I → N in PPS-L. 1 PublicationCorresponds to variant rs387906922dbSNPEnsembl.1
Natural variantiVAR_067332121I → N in PPS-L; loss of function. 1 PublicationCorresponds to variant rs387906923dbSNPEnsembl.1
Natural variantiVAR_067333184T → I in PPS-L; loss of function. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi54101.
MalaCardsiRIPK4.
MIMi263650. phenotype.
OpenTargetsiENSG00000183421.
Orphaneti1234. Bartsocas-Papas syndrome.

Chemistry databases

ChEMBLiCHEMBL6083.
GuidetoPHARMACOLOGYi2192.

Polymorphism and mutation databases

DMDMi10719883.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866131 – 832Receptor-interacting serine/threonine-protein kinase 4Add BLAST832

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki51Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki145Glycyl 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei388 – 389Cleavage2
Sitei426 – 427Cleavage2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP57078.
MaxQBiP57078.
PeptideAtlasiP57078.
PRIDEiP57078.

PTM databases

iPTMnetiP57078.
PhosphoSitePlusiP57078.

Expressioni

Gene expression databases

BgeeiENSG00000183421.
CleanExiHS_RIPK4.
GenevisibleiP57078. HS.

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
HIF1ANQ9NWT64EBI-4422308,EBI-745632
XIAPP981702EBI-4422308,EBI-517127

Protein-protein interaction databases

DIPiDIP-40722N.
IntActiP57078. 287 interactors.
MINTiMINT-142997.

Chemistry databases

BindingDBiP57078.

Structurei

3D structure databases

ProteinModelPortaliP57078.
SMRiP57078.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 286Protein kinasePROSITE-ProRule annotationAdd BLAST265
Repeati485 – 514ANK 1Add BLAST30
Repeati518 – 547ANK 2Add BLAST30
Repeati551 – 580ANK 3Add BLAST30
Repeati584 – 613ANK 4Add BLAST30
Repeati617 – 647ANK 5Add BLAST31
Repeati651 – 680ANK 6Add BLAST30
Repeati684 – 713ANK 7Add BLAST30
Repeati717 – 746ANK 8Add BLAST30
Repeati750 – 780ANK 9Add BLAST31
Repeati782 – 811ANK 10Add BLAST30

Sequence similaritiesi

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

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

GeneTreeiENSGT00550000074536.
HOGENOMiHOG000294086.
HOVERGENiHBG061582.
InParanoidiP57078.
OMAiCQHGQES.
OrthoDBiEOG091G0505.
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. 3 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 10 hits.
SM00220. S_TKc. 1 hit.
[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. AlignAdd to basket

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

        10         20         30         40         50
MEGDGGTPWA LALLRTFDAG EFTGWEKVGS GGFGQVYKVR HVHWKTWLAI
60 70 80 90 100
KCSPSLHVDD RERMELLEEA KKMEMAKFRY ILPVYGICRE PVGLVMEYME
110 120 130 140 150
TGSLEKLLAS EPLPWDLRFR IIHETAVGMN FLHCMAPPLL HLDLKPANIL
160 170 180 190 200
LDAHYHVKIS DFGLAKCNGL SHSHDLSMDG LFGTIAYLPP ERIREKSRLF
210 220 230 240 250
DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMVKVVKGH RPELPPVCRA
260 270 280 290 300
RPRACSHLIR LMQRCWQGDP RVRPTFQGNG LNGELIRQVL AALLPVTGRW
310 320 330 340 350
RSPGEGFRLE SEVIIRVTCP LSSPQEITSE TEDLCEKPDD EVKETAHDLD
360 370 380 390 400
VKSPPEPRSE VVPARLKRAS APTFDNDYSL SELLSQLDSG VSQAVEGPEE
410 420 430 440 450
LSRSSSESKL PSSGSGKRLS GVSSVDSAFS SRGSLSLSFE REPSTSDLGT
460 470 480 490 500
TDVQKKKLVD AIVSGDTSKL MKILQPQDVD LALDSGASLL HLAVEAGQEE
510 520 530 540 550
CAKWLLLNNA NPNLSNRRGS TPLHMAVERR VRGVVELLLA RKISVNAKDE
560 570 580 590 600
DQWTALHFAA QNGDESSTRL LLEKNASVNE VDFEGRTPMH VACQHGQENI
610 620 630 640 650
VRILLRRGVD VSLQGKDAWL PLHYAAWQGH LPIVKLLAKQ PGVSVNAQTL
660 670 680 690 700
DGRTPLHLAA QRGHYRVARI LIDLCSDVNV CSLLAQTPLH VAAETGHTST
710 720 730 740 750
ARLLLHRGAG KEAMTSDGYT ALHLAARNGH LATVKLLVEE KADVLARGPL
760 770 780 790 800
NQTALHLAAA HGHSEVVEEL VSADVIDLFD EQGLSALHLA AQGRHAQTVE
810 820 830
TLLRHGAHIN LQSLKFQGGH GPAATLLRRS KT
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)DescriptionActionsGraphical viewLength
Sequence conflicti714M → V in BAB56136 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03016012A → G.Corresponds to variant rs6586239dbSNPEnsembl.1
Natural variantiVAR_06733181I → N in PPS-L. 1 PublicationCorresponds to variant rs387906922dbSNPEnsembl.1
Natural variantiVAR_067332121I → N in PPS-L; loss of function. 1 PublicationCorresponds to variant rs387906923dbSNPEnsembl.1
Natural variantiVAR_030161177S → N.Corresponds to variant rs12482626dbSNPEnsembl.1
Natural variantiVAR_067333184T → I in PPS-L; loss of function. 1 Publication1
Natural variantiVAR_041050462I → N.1 PublicationCorresponds to variant rs55809511dbSNPEnsembl.1
Natural variantiVAR_041051463V → M.1 PublicationCorresponds to variant rs55645753dbSNPEnsembl.1
Natural variantiVAR_041052562N → Y.1 PublicationCorresponds to variant rs55829311dbSNPEnsembl.1
Natural variantiVAR_041053669R → H.1 PublicationCorresponds to variant rs56056485dbSNPEnsembl.1
Natural variantiVAR_041054749P → S.1 PublicationCorresponds to variant rs35537517dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004862278 – 325Missing in isoform 2. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.2. human. [P57078-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliP57078.
SMRiP57078.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-40722N.
IntActiP57078. 287 interactors.
MINTiMINT-142997.

Chemistry databases

BindingDBiP57078.
ChEMBLiCHEMBL6083.
GuidetoPHARMACOLOGYi2192.

PTM databases

iPTMnetiP57078.
PhosphoSitePlusiP57078.

Polymorphism and mutation databases

DMDMi10719883.

Proteomic databases

EPDiP57078.
MaxQBiP57078.
PeptideAtlasiP57078.
PRIDEiP57078.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

DisGeNETi54101.
GeneCardsiRIPK4.
HGNCiHGNC:496. RIPK4.
HPAiHPA021158.
MalaCardsiRIPK4.
MIMi263650. phenotype.
605706. gene.
neXtProtiNX_P57078.
OpenTargetsiENSG00000183421.
Orphaneti1234. Bartsocas-Papas syndrome.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00550000074536.
HOGENOMiHOG000294086.
HOVERGENiHBG061582.
InParanoidiP57078.
OMAiCQHGQES.
OrthoDBiEOG091G0505.
PhylomeDBiP57078.
TreeFamiTF106506.

Enzyme and pathway databases

BioCyciZFISH:HS11966-MONOMER.
SignaLinkiP57078.

Miscellaneous databases

ChiTaRSiRIPK4. human.
PROiP57078.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183421.
CleanExiHS_RIPK4.
GenevisibleiP57078. HS.

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. 3 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 10 hits.
SM00220. S_TKc. 1 hit.
[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]
ProtoNetiSearch...

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: November 30, 2016
This is version 150 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.