ID   RIPP2_HUMAN             Reviewed;         128 AA.
AC   Q5TAB7; Q5TAB6;
DT   23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 125.
DE   RecName: Full=Protein ripply2;
GN   Name=RIPPLY2; Synonyms=C6orf159;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1] {ECO:0000312|EMBL:AL139232}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [2] {ECO:0000312|EMBL:EAW48651.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000305, ECO:0000312|EMBL:AAI30461.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain {ECO:0000312|EMBL:AAI30461.1};
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] {ECO:0000305}
RP   IDENTIFICATION AS RIPPLY2.
RX   PubMed=16326386; DOI=10.1016/j.devcel.2005.09.021;
RA   Kawamura A., Koshida S., Hijikata H., Ohbayashi A., Kondoh H., Takada S.;
RT   "Groucho-associated transcriptional repressor ripply1 is required for
RT   proper transition from the presomitic mesoderm to somites.";
RL   Dev. Cell 9:735-744(2005).
RN   [5]
RP   INVOLVEMENT IN SCDO6.
RX   PubMed=25343988; DOI=10.1093/hmg/ddu534;
RA   McInerney-Leo A.M., Sparrow D.B., Harris J.E., Gardiner B.B.,
RA   Marshall M.S., O'Reilly V.C., Shi H., Brown M.A., Leo P.J., Zankl A.,
RA   Dunwoodie S.L., Duncan E.L.;
RT   "Compound heterozygous mutations in RIPPLY2 associated with vertebral
RT   segmentation defects.";
RL   Hum. Mol. Genet. 24:1234-1242(2015).
CC   -!- FUNCTION: Plays a role in somitogenesis. Required for somite
CC       segregation and establishment of rostrocaudal polarity in somites (By
CC       similarity). {ECO:0000250|UniProtKB:Q2WG76}.
CC   -!- INTERACTION:
CC       Q5TAB7; Q5T686: AVPI1; NbExp=3; IntAct=EBI-10246897, EBI-8640233;
CC       Q5TAB7; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-10246897, EBI-18036948;
CC       Q5TAB7; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-10246897, EBI-21603100;
CC       Q5TAB7; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-10246897, EBI-712073;
CC       Q5TAB7; P42858: HTT; NbExp=6; IntAct=EBI-10246897, EBI-466029;
CC       Q5TAB7; Q8N6L0: KASH5; NbExp=8; IntAct=EBI-10246897, EBI-749265;
CC       Q5TAB7; P17568: NDUFB7; NbExp=3; IntAct=EBI-10246897, EBI-1246238;
CC       Q5TAB7; P40425: PBX2; NbExp=5; IntAct=EBI-10246897, EBI-348489;
CC       Q5TAB7; Q9BYU1: PBX4; NbExp=5; IntAct=EBI-10246897, EBI-10302990;
CC       Q5TAB7; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-10246897, EBI-5235340;
CC       Q5TAB7; Q8N205: SYNE4; NbExp=3; IntAct=EBI-10246897, EBI-7131783;
CC       Q5TAB7; Q05BK6: TFG; NbExp=3; IntAct=EBI-10246897, EBI-10246902;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q2WG80}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1 {ECO:0000269|PubMed:14574404, ECO:0000269|PubMed:15489334};
CC         IsoId=Q5TAB7-1; Sequence=Displayed;
CC       Name=2 {ECO:0000269|PubMed:14574404};
CC         IsoId=Q5TAB7-2; Sequence=VSP_052556;
CC   -!- DOMAIN: The ripply homology domain is required for transcriptional
CC       repression. {ECO:0000250}.
CC   -!- DOMAIN: The WRPW motif is required for binding to tle/groucho proteins.
CC       {ECO:0000250|UniProtKB:Q2WG80}.
CC   -!- DISEASE: Spondylocostal dysostosis 6, autosomal recessive (SCDO6)
CC       [MIM:616566]: A form of spondylocostal dysostosis, a condition of
CC       variable severity associated with vertebral and rib segmentation
CC       defects. The main skeletal malformations include fusion of vertebrae,
CC       hemivertebrae, fusion of certain ribs, and other rib malformations.
CC       Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and
CC       lordosis) is a natural consequence of the malformation and leads to a
CC       dwarf-like appearance. As the thorax is small, infants frequently have
CC       respiratory insufficiency and repeated respiratory infections resulting
CC       in life-threatening complications in the first year of life.
CC       {ECO:0000269|PubMed:25343988}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the ripply family. {ECO:0000305}.
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DR   EMBL; AL139232; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471051; EAW48651.1; -; Genomic_DNA.
DR   EMBL; BC130460; AAI30461.1; -; mRNA.
DR   EMBL; BC132968; AAI32969.1; -; mRNA.
DR   CCDS; CCDS34493.1; -. [Q5TAB7-1]
DR   RefSeq; NP_001009994.1; NM_001009994.2. [Q5TAB7-1]
DR   AlphaFoldDB; Q5TAB7; -.
DR   BioGRID; 126411; 19.
DR   IntAct; Q5TAB7; 22.
DR   STRING; 9606.ENSP00000358703; -.
DR   iPTMnet; Q5TAB7; -.
DR   PhosphoSitePlus; Q5TAB7; -.
DR   BioMuta; RIPPLY2; -.
DR   DMDM; 74745808; -.
DR   MassIVE; Q5TAB7; -.
DR   PaxDb; Q5TAB7; -.
DR   PeptideAtlas; Q5TAB7; -.
DR   PRIDE; Q5TAB7; -.
DR   Antibodypedia; 57637; 63 antibodies from 10 providers.
DR   DNASU; 134701; -.
DR   Ensembl; ENST00000369687.2; ENSP00000358701.1; ENSG00000203877.9. [Q5TAB7-2]
DR   Ensembl; ENST00000369689.6; ENSP00000358703.1; ENSG00000203877.9. [Q5TAB7-1]
DR   GeneID; 134701; -.
DR   KEGG; hsa:134701; -.
DR   MANE-Select; ENST00000369689.6; ENSP00000358703.1; NM_001009994.3; NP_001009994.1.
DR   UCSC; uc003pke.5; human. [Q5TAB7-1]
DR   CTD; 134701; -.
DR   DisGeNET; 134701; -.
DR   GeneCards; RIPPLY2; -.
DR   GeneReviews; RIPPLY2; -.
DR   HGNC; HGNC:21390; RIPPLY2.
DR   HPA; ENSG00000203877; Tissue enhanced (brain, choroid plexus, pituitary gland).
DR   MalaCards; RIPPLY2; -.
DR   MIM; 609891; gene.
DR   MIM; 616566; phenotype.
DR   neXtProt; NX_Q5TAB7; -.
DR   OpenTargets; ENSG00000203877; -.
DR   Orphanet; 2311; Autosomal recessive spondylocostal dysostosis.
DR   PharmGKB; PA162401349; -.
DR   VEuPathDB; HostDB:ENSG00000203877; -.
DR   eggNOG; ENOG502S6U6; Eukaryota.
DR   GeneTree; ENSGT00940000161538; -.
DR   HOGENOM; CLU_117697_1_1_1; -.
DR   InParanoid; Q5TAB7; -.
DR   OMA; LWRPWNK; -.
DR   OrthoDB; 1552301at2759; -.
DR   PhylomeDB; Q5TAB7; -.
DR   TreeFam; TF336045; -.
DR   PathwayCommons; Q5TAB7; -.
DR   SignaLink; Q5TAB7; -.
DR   BioGRID-ORCS; 134701; 5 hits in 1060 CRISPR screens.
DR   ChiTaRS; RIPPLY2; human.
DR   GenomeRNAi; 134701; -.
DR   Pharos; Q5TAB7; Tdark.
DR   PRO; PR:Q5TAB7; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q5TAB7; protein.
DR   Bgee; ENSG00000203877; Expressed in cerebellar hemisphere and 111 other tissues.
DR   Genevisible; Q5TAB7; HS.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0060349; P:bone morphogenesis; IEA:Ensembl.
DR   GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR   GO; GO:0009880; P:embryonic pattern specification; IBA:GO_Central.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR   GO; GO:0001503; P:ossification; IEA:Ensembl.
DR   GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR   GO; GO:0032525; P:somite rostral/caudal axis specification; ISS:UniProtKB.
DR   GO; GO:0001756; P:somitogenesis; ISS:UniProtKB.
DR   InterPro; IPR028127; Ripply_fam.
DR   PANTHER; PTHR16770; PTHR16770; 1.
DR   Pfam; PF14998; Ripply; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Developmental protein; Dwarfism; Nucleus;
KW   Reference proteome.
FT   CHAIN           1..128
FT                   /note="Protein ripply2"
FT                   /id="PRO_0000307759"
FT   REGION          1..63
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          77..112
FT                   /note="Ripply homology domain"
FT                   /evidence="ECO:0000255"
FT   MOTIF           37..40
FT                   /note="WRPW motif"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..58
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14574404"
FT                   /id="VSP_052556"
SQ   SEQUENCE   128 AA;  13906 MW;  F1ED3019B4E1DA02 CRC64;
     MENAGGAEGT ESGAAACAAT DGPTRRAGAD SGYAGFWRPW VDAGGKKEEE TPNHAAEAMP
     DGPGMTAASG KLYQFRHPVR LFWPKSKCYD YLYQEAEALL KNFPIQATIS FYEDSDSEDE
     IEDLTCEN