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Protein

Receptor-interacting serine/threonine-protein kinase 4

Gene

RIPK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionKinase, Receptor, Serine/threonine-protein kinase, Transferase
LigandATP-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
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000183421.11
HGNCiHGNC:496 RIPK4
MIMi605706 gene
neXtProtiNX_P57078

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Popliteal pterygium syndrome, lethal type (PPS-L)2 Publications
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 dbSNP:rs387906922EnsemblClinVar.1
Natural variantiVAR_067332121I → N in PPS-L; loss of function. 1 PublicationCorresponds to variant dbSNP:rs387906923EnsemblClinVar.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 – 389Cleavage1 Publication2
Sitei426 – 427Cleavage1 Publication2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP57078
MaxQBiP57078
PeptideAtlasiP57078
PRIDEiP57078
ProteomicsDBi56989
56990 [P57078-2]

PTM databases

iPTMnetiP57078
PhosphoSitePlusiP57078

Expressioni

Gene expression databases

BgeeiENSG00000183421
CleanExiHS_RIPK4
GenevisibleiP57078 HS

Organism-specific databases

HPAiHPA030942

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

Show more details

Protein-protein interaction databases

DIPiDIP-40722N
IntActiP57078, 294 interactors

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

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

GeneTreeiENSGT00550000074536
HOGENOMiHOG000294086
HOVERGENiHBG061582
InParanoidiP57078
OMAiACQHGQE
OrthoDBiEOG091G0505
PhylomeDBiP57078
TreeFamiTF106506

Family and domain databases

CDDicd00204 ANK, 4 hits
Gene3Di1.25.40.20, 4 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF12796 Ank_2, 3 hits
PF00069 Pkinase, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 10 hits
SM00220 S_TKc, 1 hit
SUPFAMiSSF48403 SSF48403, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

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 dbSNP:rs6586239EnsemblClinVar.1
Natural variantiVAR_06733181I → N in PPS-L. 1 PublicationCorresponds to variant dbSNP:rs387906922EnsemblClinVar.1
Natural variantiVAR_067332121I → N in PPS-L; loss of function. 1 PublicationCorresponds to variant dbSNP:rs387906923EnsemblClinVar.1
Natural variantiVAR_030161177S → N. Corresponds to variant dbSNP:rs12482626Ensembl.1
Natural variantiVAR_067333184T → I in PPS-L; loss of function. 1 Publication1
Natural variantiVAR_041050462I → N1 PublicationCorresponds to variant dbSNP:rs55809511Ensembl.1
Natural variantiVAR_041051463V → M1 PublicationCorresponds to variant dbSNP:rs55645753Ensembl.1
Natural variantiVAR_041052562N → Y1 PublicationCorresponds to variant dbSNP:rs55829311Ensembl.1
Natural variantiVAR_041053669R → H1 PublicationCorresponds to variant dbSNP:rs56056485Ensembl.1
Natural variantiVAR_041054749P → S1 PublicationCorresponds to variant dbSNP:rs35537517Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiRIPK4_HUMAN
AccessioniPrimary (citable) accession number: P57078
Secondary accession number(s): Q96KH0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: June 20, 2018
This is version 162 of the entry and version 1 of the sequence. See 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

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