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Receptor-interacting serine/threonine-protein kinase 4 (EC 2.7.11.1) (Ankyrin repeat domain-containing protein 3) (PKC-delta-interacting protein kinase)

 RIPK4_HUMAN             Reviewed;         832 AA.
P57078; Q96KH0;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-DEC-2000, sequence version 1.
25-APR-2018, entry version 161.
RecName: Full=Receptor-interacting serine/threonine-protein kinase 4;
EC=2.7.11.1;
AltName: Full=Ankyrin repeat domain-containing protein 3;
AltName: Full=PKC-delta-interacting protein kinase;
Name=RIPK4; Synonyms=ANKRD3, DIK;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Fetal kidney, and Fetal lung;
Shimizu N., Kudoh J., Shibuya K.;
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=10830953; DOI=10.1038/35012518;
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.;
"The DNA sequence of human chromosome 21.";
Nature 405:311-319(2000).
[3]
PROTEOLYTIC CLEAVAGE AT ASP-388 AND ASP-426, INTERACTION WITH TRAF1;
TRAF2; TRAF3 AND TRAF5, AND FUNCTION.
PubMed=12446564; DOI=10.1093/embo-reports/kvf236;
Meylan E., Martinon F., Thome M., Gschwendt M., Tschopp J.;
"RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates
NF-kappa B and is processed during apoptosis.";
EMBO Rep. 3:1201-1208(2002).
[4]
UBIQUITINATION AT LYS-51 AND LYS-145, UBIQUITINATION BY BIRC2/C-IAP1
AND BIRC3/C-IAP2, AND INTERACTION WITH BIRC2/C-IAP1; BIRC3/C-IAP2 AND
XIAP/BIRC4.
PubMed=21931591; DOI=10.1371/journal.pone.0022356;
Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R.,
De Medts J., Gevaert K., Declercq W., Vandenabeele P.;
"cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin
chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).";
PLoS ONE 6:E22356-E22356(2011).
[5]
FUNCTION, AND VARIANT PPS-L ASN-81.
PubMed=22197488; DOI=10.1016/j.ajhg.2011.11.013;
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.;
"Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome
locus.";
Am. J. Hum. Genet. 90:69-75(2012).
[6]
VARIANTS [LARGE SCALE ANALYSIS] ASN-462; MET-463; TYR-562; HIS-669 AND
SER-749.
PubMed=17344846; DOI=10.1038/nature05610;
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.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
[7]
VARIANTS PPS-L ASN-121 AND ILE-184, AND CHARACTERIZATION OF VARIANTS
PPS-L ASN-121 AND ILE-184.
PubMed=22197489; DOI=10.1016/j.ajhg.2011.11.014;
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.;
"Mutations in RIPK4 cause the autosomal-recessive form of popliteal
pterygium syndrome.";
Am. J. Hum. Genet. 90:76-85(2012).
-!- FUNCTION: Involved in stratified epithelial development. It is a
direct transcriptional target of TP63. Plays a role in NF-kappa-B
activation. {ECO:0000269|PubMed:12446564,
ECO:0000269|PubMed:22197488}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- SUBUNIT: Interacts with PRKCB (By similarity). Interacts with
TRAF1, TRAF2, TRAF3 and TRAF5. Interacts with BIRC2/c-IAP1,
BIRC3/c-IAP2 and XIAP/BIRC4. {ECO:0000250,
ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:21931591}.
-!- INTERACTION:
Q13490:BIRC2; NbExp=3; IntAct=EBI-4422308, EBI-514538;
Q13489:BIRC3; NbExp=3; IntAct=EBI-4422308, EBI-517709;
O14641:DVL2; NbExp=4; IntAct=EBI-4422308, EBI-740850;
Q9NWT6:HIF1AN; NbExp=4; IntAct=EBI-4422308, EBI-745632;
P98170:XIAP; NbExp=2; IntAct=EBI-4422308, EBI-517127;
-!- SUBCELLULAR LOCATION: Cytoplasm. Membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P57078-1; Sequence=Displayed;
Name=2;
IsoId=P57078-2; Sequence=VSP_004862;
-!- PTM: May be phosphorylated by MAP3K2 and MAP3K3. {ECO:0000250}.
-!- PTM: Proteolytically cleaved by during Fas-induced apoptosis.
Cleavage at Asp-388 and Asp-426. {ECO:0000269|PubMed:12446564}.
-!- PTM: Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by
BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-
B. {ECO:0000269|PubMed:21931591}.
-!- 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.
{ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:22197489}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
protein kinase family. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AB047783; BAB56136.1; -; mRNA.
EMBL; AP001743; BAA95526.1; -; Genomic_DNA.
CCDS; CCDS13675.1; -. [P57078-2]
UniGene; Hs.517310; -.
ProteinModelPortal; P57078; -.
SMR; P57078; -.
DIP; DIP-40722N; -.
IntAct; P57078; 294.
BindingDB; P57078; -.
ChEMBL; CHEMBL6083; -.
GuidetoPHARMACOLOGY; 2192; -.
iPTMnet; P57078; -.
PhosphoSitePlus; P57078; -.
DMDM; 10719883; -.
EPD; P57078; -.
MaxQB; P57078; -.
PeptideAtlas; P57078; -.
PRIDE; P57078; -.
Ensembl; ENST00000332512; ENSP00000332454; ENSG00000183421. [P57078-2]
Ensembl; ENST00000352483; ENSP00000330161; ENSG00000183421. [P57078-1]
UCSC; uc002yzn.2; human. [P57078-1]
DisGeNET; 54101; -.
EuPathDB; HostDB:ENSG00000183421.11; -.
GeneCards; RIPK4; -.
HGNC; HGNC:496; RIPK4.
MalaCards; RIPK4; -.
MIM; 263650; phenotype.
MIM; 605706; gene.
neXtProt; NX_P57078; -.
OpenTargets; ENSG00000183421; -.
Orphanet; 1234; Bartsocas-Papas syndrome.
GeneTree; ENSGT00550000074536; -.
HOGENOM; HOG000294086; -.
HOVERGEN; HBG061582; -.
InParanoid; P57078; -.
OMA; ACQHGQE; -.
OrthoDB; EOG091G0505; -.
PhylomeDB; P57078; -.
TreeFam; TF106506; -.
SignaLink; P57078; -.
ChiTaRS; RIPK4; human.
PRO; PR:P57078; -.
Proteomes; UP000005640; Chromosome 21.
Bgee; ENSG00000183421; -.
CleanEx; HS_RIPK4; -.
Genevisible; P57078; HS.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
GO; GO:0002009; P:morphogenesis of an epithelium; IMP:UniProtKB.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
CDD; cd00204; ANK; 4.
Gene3D; 1.25.40.20; -; 4.
InterPro; IPR002110; Ankyrin_rpt.
InterPro; IPR020683; Ankyrin_rpt-contain_dom.
InterPro; IPR036770; Ankyrin_rpt-contain_sf.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF12796; Ank_2; 3.
Pfam; PF00069; Pkinase; 1.
PRINTS; PR01415; ANKYRIN.
SMART; SM00248; ANK; 10.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF48403; SSF48403; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS50297; ANK_REP_REGION; 1.
PROSITE; PS50088; ANK_REPEAT; 9.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
Alternative splicing; ANK repeat; ATP-binding; Complete proteome;
Cytoplasm; Disease mutation; Isopeptide bond; Kinase; Membrane;
Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor;
Reference proteome; Repeat; Serine/threonine-protein kinase;
Transferase; Ubl conjugation.
CHAIN 1 832 Receptor-interacting serine/threonine-
protein kinase 4.
/FTId=PRO_0000086613.
DOMAIN 22 286 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REPEAT 485 514 ANK 1.
REPEAT 518 547 ANK 2.
REPEAT 551 580 ANK 3.
REPEAT 584 613 ANK 4.
REPEAT 617 647 ANK 5.
REPEAT 651 680 ANK 6.
REPEAT 684 713 ANK 7.
REPEAT 717 746 ANK 8.
REPEAT 750 780 ANK 9.
REPEAT 782 811 ANK 10.
NP_BIND 28 36 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ACT_SITE 143 143 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 51 51 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
SITE 388 389 Cleavage. {ECO:0000269|PubMed:12446564}.
SITE 426 427 Cleavage. {ECO:0000269|PubMed:12446564}.
CROSSLNK 51 51 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000269|PubMed:21931591}.
CROSSLNK 145 145 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000269|PubMed:21931591}.
VAR_SEQ 278 325 Missing (in isoform 2).
{ECO:0000303|Ref.1}.
/FTId=VSP_004862.
VARIANT 12 12 A -> G (in dbSNP:rs6586239).
/FTId=VAR_030160.
VARIANT 81 81 I -> N (in PPS-L; dbSNP:rs387906922).
{ECO:0000269|PubMed:22197488}.
/FTId=VAR_067331.
VARIANT 121 121 I -> N (in PPS-L; loss of function;
dbSNP:rs387906923).
{ECO:0000269|PubMed:22197489}.
/FTId=VAR_067332.
VARIANT 177 177 S -> N (in dbSNP:rs12482626).
/FTId=VAR_030161.
VARIANT 184 184 T -> I (in PPS-L; loss of function).
{ECO:0000269|PubMed:22197489}.
/FTId=VAR_067333.
VARIANT 462 462 I -> N (in dbSNP:rs55809511).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041050.
VARIANT 463 463 V -> M (in dbSNP:rs55645753).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041051.
VARIANT 562 562 N -> Y (in dbSNP:rs55829311).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041052.
VARIANT 669 669 R -> H (in dbSNP:rs56056485).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041053.
VARIANT 749 749 P -> S (in dbSNP:rs35537517).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041054.
CONFLICT 714 714 M -> V (in Ref. 1; BAB56136).
{ECO:0000305}.
SEQUENCE 832 AA; 91611 MW; 5D8FFFD5F04F7ECB CRC64;
MEGDGGTPWA LALLRTFDAG EFTGWEKVGS GGFGQVYKVR HVHWKTWLAI KCSPSLHVDD
RERMELLEEA KKMEMAKFRY ILPVYGICRE PVGLVMEYME TGSLEKLLAS EPLPWDLRFR
IIHETAVGMN FLHCMAPPLL HLDLKPANIL LDAHYHVKIS DFGLAKCNGL SHSHDLSMDG
LFGTIAYLPP ERIREKSRLF DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMVKVVKGH
RPELPPVCRA RPRACSHLIR LMQRCWQGDP RVRPTFQGNG LNGELIRQVL AALLPVTGRW
RSPGEGFRLE SEVIIRVTCP LSSPQEITSE TEDLCEKPDD EVKETAHDLD VKSPPEPRSE
VVPARLKRAS APTFDNDYSL SELLSQLDSG VSQAVEGPEE LSRSSSESKL PSSGSGKRLS
GVSSVDSAFS SRGSLSLSFE REPSTSDLGT TDVQKKKLVD AIVSGDTSKL MKILQPQDVD
LALDSGASLL HLAVEAGQEE CAKWLLLNNA NPNLSNRRGS TPLHMAVERR VRGVVELLLA
RKISVNAKDE DQWTALHFAA QNGDESSTRL LLEKNASVNE VDFEGRTPMH VACQHGQENI
VRILLRRGVD VSLQGKDAWL PLHYAAWQGH LPIVKLLAKQ PGVSVNAQTL DGRTPLHLAA
QRGHYRVARI LIDLCSDVNV CSLLAQTPLH VAAETGHTST ARLLLHRGAG KEAMTSDGYT
ALHLAARNGH LATVKLLVEE KADVLARGPL NQTALHLAAA HGHSEVVEEL VSADVIDLFD
EQGLSALHLA AQGRHAQTVE TLLRHGAHIN LQSLKFQGGH GPAATLLRRS KT


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