ID RIPK4_MOUSE Reviewed; 786 AA.
AC Q9ERK0; Q3UM04;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 27-MAR-2024, entry version 165.
DE RecName: Full=Receptor-interacting serine/threonine-protein kinase 4;
DE EC=2.7.11.1;
DE AltName: Full=Ankyrin repeat domain-containing protein 3;
DE AltName: Full=PKC-associated protein kinase;
DE AltName: Full=PKC-regulated protein kinase;
GN Name=Ripk4; Synonyms=Ankrd3, Pkk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PRKCB, PHOSPHORYLATION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ;
RX PubMed=11278382; DOI=10.1074/jbc.m008069200;
RA Chen L., Haider K., Ponda M., Cariappa A., Rowitch D., Pillai S.;
RT "Protein kinase C-associated kinase (PKK), a novel membrane-associated,
RT ankyrin repeat-containing protein kinase.";
RL J. Biol. Chem. 276:21737-21744(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEOLYTIC CLEAVAGE AT ASP-342 AND ASP-380, INTERACTION WITH TRAF1; TRAF2;
RP TRAF3 AND TRAF5, AND FUNCTION.
RX PubMed=12446564; DOI=10.1093/embo-reports/kvf236;
RA Meylan E., Martinon F., Thome M., Gschwendt M., Tschopp J.;
RT "RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-
RT kappa B and is processed during apoptosis.";
RL EMBO Rep. 3:1201-1208(2002).
RN [5]
RP PHOSPHORYLATION.
RX PubMed=12676934; DOI=10.1074/jbc.m301575200;
RA Moran S.T., Haider K., Ow Y., Milton P., Chen L., Pillai S.;
RT "Protein kinase C-associated kinase can activate NFkappaB in both a kinase-
RT dependent and a kinase-independent manner.";
RL J. Biol. Chem. 278:21526-21533(2003).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22197488; DOI=10.1016/j.ajhg.2011.11.013;
RA Mitchell K., O'Sullivan J., Missero C., Blair E., Richardson R.,
RA Anderson B., Antonini D., Murray J.C., Shanske A.L., Schutte B.C.,
RA Romano R.A., Sinha S., Bhaskar S.S., Black G.C., Dixon J., Dixon M.J.;
RT "Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus.";
RL Am. J. Hum. Genet. 90:69-75(2012).
CC -!- FUNCTION: Involved in stratified epithelial development (By
CC similarity). It is a direct transcriptional target of TP63. Plays a
CC role in NF-kappa-B activation. {ECO:0000250,
CC ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:22197488}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with PRKCB. Interacts with TRAF1, TRAF2, TRAF3 and
CC TRAF5. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4.
CC {ECO:0000269|PubMed:11278382, ECO:0000269|PubMed:12446564}.
CC -!- INTERACTION:
CC Q9ERK0; Q6Q0C0: TRAF7; Xeno; NbExp=2; IntAct=EBI-6116422, EBI-307556;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Note=At steady state, a minor portion of this protein is membrane-
CC associated. The major portion is cytoplasmic.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with an abundant expression
CC in the thymus, bone marrow, pro-B, pre-B and immature B cells and a
CC weak expression in the spleen. {ECO:0000269|PubMed:11278382}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 10.5 dpc at diverse locations
CC including the embryonic forebrain, otic vesicle, branchial arches,
CC primitive gut, and genitourinary system. Transient expression in the
CC ventral neural tube at 12.5 dpc. By 14.5 dpc, strong expression
CC throughout the gastrointestinal tract was observed in the luminal
CC tissues of the esophagus, stomach, duodenum, and intestines, as well as
CC transient expression in the skin. Not expressed in kidney.
CC {ECO:0000269|PubMed:11278382}.
CC -!- PTM: May be phosphorylated by MAP3K2 and MAP3K3.
CC {ECO:0000269|PubMed:11278382, ECO:0000269|PubMed:12676934}.
CC -!- PTM: Proteolytically cleaved by during Fas-induced apoptosis. Cleavage
CC at Asp-342 and Asp-380. {ECO:0000269|PubMed:12446564}.
CC -!- PTM: Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by
CC BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AF302127; AAG30871.2; -; mRNA.
DR EMBL; AK145203; BAE26294.1; -; mRNA.
DR EMBL; BC057871; AAH57871.1; -; mRNA.
DR CCDS; CCDS28360.1; -.
DR RefSeq; NP_076152.2; NM_023663.6.
DR PDB; 5WNI; X-ray; 2.65 A; A=1-342.
DR PDB; 5WNJ; X-ray; 2.55 A; A=1-342.
DR PDB; 5WNK; X-ray; 3.11 A; A=1-342.
DR PDB; 5WNL; X-ray; 2.50 A; A=1-342.
DR PDB; 5WNM; X-ray; 2.60 A; A=1-342.
DR PDBsum; 5WNI; -.
DR PDBsum; 5WNJ; -.
DR PDBsum; 5WNK; -.
DR PDBsum; 5WNL; -.
DR PDBsum; 5WNM; -.
DR AlphaFoldDB; Q9ERK0; -.
DR SMR; Q9ERK0; -.
DR IntAct; Q9ERK0; 1.
DR STRING; 10090.ENSMUSP00000019386; -.
DR iPTMnet; Q9ERK0; -.
DR PhosphoSitePlus; Q9ERK0; -.
DR PaxDb; 10090-ENSMUSP00000019386; -.
DR ProteomicsDB; 253312; -.
DR Antibodypedia; 9243; 323 antibodies from 27 providers.
DR DNASU; 72388; -.
DR Ensembl; ENSMUST00000019386.10; ENSMUSP00000019386.9; ENSMUSG00000005251.16.
DR GeneID; 72388; -.
DR KEGG; mmu:72388; -.
DR UCSC; uc008adn.1; mouse.
DR AGR; MGI:1919638; -.
DR CTD; 54101; -.
DR MGI; MGI:1919638; Ripk4.
DR VEuPathDB; HostDB:ENSMUSG00000005251; -.
DR eggNOG; KOG0192; Eukaryota.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000159908; -.
DR HOGENOM; CLU_015188_0_0_1; -.
DR InParanoid; Q9ERK0; -.
DR OMA; HSKENTC; -.
DR OrthoDB; 5295000at2759; -.
DR PhylomeDB; Q9ERK0; -.
DR TreeFam; TF106506; -.
DR BioGRID-ORCS; 72388; 2 hits in 79 CRISPR screens.
DR ChiTaRS; Ripk4; mouse.
DR PRO; PR:Q9ERK0; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9ERK0; Protein.
DR Bgee; ENSMUSG00000005251; Expressed in urinary bladder urothelium and 199 other cell types or tissues.
DR Genevisible; Q9ERK0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0002009; P:morphogenesis of an epithelium; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd14025; STKc_RIP4_like; 1.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 3.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24198; ANKYRIN REPEAT AND PROTEIN KINASE DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR24198:SF65; RECEPTOR-INTERACTING SERINE_THREONINE-PROTEIN KINASE 4; 1.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF13637; Ank_4; 2.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 10.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 9.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; ATP-binding; Cytoplasm; Isopeptide bond; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..786
FT /note="Receptor-interacting serine/threonine-protein kinase
FT 4"
FT /id="PRO_0000273726"
FT DOMAIN 22..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 439..468
FT /note="ANK 1"
FT REPEAT 472..501
FT /note="ANK 2"
FT REPEAT 505..534
FT /note="ANK 3"
FT REPEAT 538..567
FT /note="ANK 4"
FT REPEAT 571..601
FT /note="ANK 5"
FT REPEAT 605..634
FT /note="ANK 6"
FT REPEAT 638..667
FT /note="ANK 7"
FT REPEAT 671..700
FT /note="ANK 8"
FT REPEAT 704..734
FT /note="ANK 9"
FT REPEAT 736..765
FT /note="ANK 10"
FT REGION 293..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 143
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 28..36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 51
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 342..343
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:12446564"
FT SITE 380..381
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:12446564"
FT CROSSLNK 51
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P57078"
FT CROSSLNK 145
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P57078"
FT CONFLICT 718
FT /note="S -> T (in Ref. 2; BAE26294)"
FT /evidence="ECO:0000305"
FT HELIX 10..13
FT /evidence="ECO:0007829|PDB:5WNI"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:5WNL"
FT TURN 42..45
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:5WNJ"
FT HELIX 60..75
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:5WNL"
FT TURN 89..92
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:5WNM"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 115..134
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:5WNL"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:5WNL"
FT TURN 184..187
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 190..194
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 202..218
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 229..237
FT /evidence="ECO:0007829|PDB:5WNL"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 252..265
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:5WNL"
FT HELIX 276..286
FT /evidence="ECO:0007829|PDB:5WNL"
SQ SEQUENCE 786 AA; 86613 MW; 66CE2C25EE96A40C CRC64;
MEGEGRGRWA LGLLRTFDAG EFAGWEKVGS GGFGQVYKVR HVHWKTWLAI KCSPSLHVDD
RERMELLEEA KKMEMAKFRY ILPVYGICQE PVGLVMEYME TGSLEKLLAS EPLPWDLRFR
IVHETAVGMN FLHCMSPPLL HLDLKPANIL LDAHYHVKIS DFGLAKCNGM SHSHDLSMDG
LFGTIAYLPP ERIREKSRLF DTKHDVYSFA IVIWGVLTQK KPFADEKNIL HIMMKVVKGH
RPELPPICRP RPRACASLIG LMQRCWHADP QVRPTFQEIT SETEDLCEKP DEEVKDLAHE
PGEKSSLESK SEARPESSRL KRASAPPFDN DCSLSELLSQ LDSGISQTLE GPEELSRSSS
ECKLPSSSSG KRLSGVSSVD SAFSSRGSLS LSFEREASTG DLGPTDIQKK KLVDAIISGD
TSRLMKILQP QDVDLVLDSS ASLLHLAVEA GQEECVKWLL LNNANPNLTN RKGSTPLHMA
VERKGRGIVE LLLARKTSVN AKDEDQWTAL HFAAQNGDEA STRLLLEKNA SVNEVDFEGR
TPMHVACQHG QENIVRTLLR RGVDVGLQGK DAWLPLHYAA WQGHLPIVKL LAKQPGVSVN
AQTLDGRTPL HLAAQRGHYR VARILIDLCS DVNICSLQAQ TPLHVAAETG HTSTARLLLH
RGAGKEALTS EGYTALHLAA QNGHLATVKL LIEEKADVMA RGPLNQTALH LAAARGHSEV
VEELVSADLI DLSDEQGLSA LHLAAQGRHS QTVETLLKHG AHINLQSLKF QGGQSSAATL
LRRSKT
//
