RSPH3_HUMAN
ID RSPH3_HUMAN Reviewed; 560 AA.
AC Q86UC2; Q96LQ5; Q96LX2; Q9BX75;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Radial spoke head protein 3 homolog;
DE AltName: Full=A-kinase anchor protein RSPH3;
DE AltName: Full=Radial spoke head-like protein 2;
GN Name=RSPH3; Synonyms=RSHL2, RSP3;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 66-560 (ISOFORM 2).
RC TISSUE=Epithelium, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 52-560 (ISOFORM 1).
RC TISSUE=Testis;
RA DeKorte M., Carr D.W.;
RT "Molecular characterization of the human radial spoke protein 3 as an A-
RT kinase anchoring protein.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, SUBUNIT, AND PHOSPHORYLATION AT THR-286.
RX PubMed=19684019; DOI=10.1074/jbc.m109.048181;
RA Jivan A., Earnest S., Juang Y.C., Cobb M.H.;
RT "Radial spoke protein 3 is a mammalian protein kinase A-anchoring protein
RT that binds ERK1/2.";
RL J. Biol. Chem. 284:29437-29445(2009).
RN [7]
RP INVOLVEMENT IN CILD32.
RX PubMed=26073779; DOI=10.1016/j.ajhg.2015.05.004;
RA Jeanson L., Copin B., Papon J.F., Dastot-Le Moal F., Duquesnoy P.,
RA Montantin G., Cadranel J., Corvol H., Coste A., Desir J., Souayah A.,
RA Kott E., Collot N., Tissier S., Louis B., Tamalet A., de Blic J.,
RA Clement A., Escudier E., Amselem S., Legendre M.;
RT "RSPH3 mutations cause Primary ciliary dyskinesia with central-complex
RT defects and a near absence of radial spokes.";
RL Am. J. Hum. Genet. 97:153-162(2015).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=27120127; DOI=10.1002/humu.23005;
RA Jeanson L., Thomas L., Copin B., Coste A., Sermet-Gaudelus I.,
RA Dastot-Le Moal F., Duquesnoy P., Montantin G., Collot N., Tissier S.,
RA Papon J.F., Clement A., Louis B., Escudier E., Amselem S., Legendre M.;
RT "Mutations in GAS8, a gene encoding a nexin-dynein regulatory complex
RT subunit, cause primary ciliary dyskinesia with axonemal disorganization.";
RL Hum. Mutat. 37:776-785(2016).
CC -!- FUNCTION: Functions as a protein kinase A-anchoring protein that
CC scaffolds the cAMP-dependent protein kinase holoenzyme. May serve as a
CC point of convergence for MAPK and PKA signaling in cilia.
CC {ECO:0000269|PubMed:19684019}.
CC -!- SUBUNIT: Interacts with phosphorylated MAPK1. Interacts with MEK1.
CC Interacts with PKA regulatory subunits PRKAR1A and PRKAR1B.
CC {ECO:0000269|PubMed:19684019}.
CC -!- INTERACTION:
CC Q86UC2; Q9C005: DPY30; NbExp=3; IntAct=EBI-6873025, EBI-744973;
CC Q86UC2; Q9H5Z6-2: FAM124B; NbExp=3; IntAct=EBI-6873025, EBI-11986315;
CC Q86UC2; P40692: MLH1; NbExp=3; IntAct=EBI-6873025, EBI-744248;
CC Q86UC2; P10644: PRKAR1A; NbExp=3; IntAct=EBI-6873025, EBI-476431;
CC Q86UC2; Q96C74: ROPN1L; NbExp=7; IntAct=EBI-6873025, EBI-9033237;
CC Q86UC2; Q9UHP6: RSPH14; NbExp=3; IntAct=EBI-6873025, EBI-748350;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000250|UniProtKB:P12759}. Cell projection, cilium
CC {ECO:0000269|PubMed:27120127}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86UC2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86UC2-2; Sequence=VSP_030128;
CC -!- DISEASE: Ciliary dyskinesia, primary, 32 (CILD32) [MIM:616481]: A
CC disorder characterized by abnormalities of motile cilia. Respiratory
CC infections leading to chronic inflammation and bronchiectasis are
CC recurrent, due to defects in the respiratory cilia.
CC {ECO:0000269|PubMed:26073779}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the flagellar radial spoke RSP3 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK26432.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB71544.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK057655; BAB71544.1; ALT_INIT; mRNA.
DR EMBL; AK057931; BAB71615.1; -; mRNA.
DR EMBL; AL035530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47643.1; -; Genomic_DNA.
DR EMBL; BC050604; AAH50604.1; -; mRNA.
DR EMBL; AF353618; AAK26432.1; ALT_INIT; mRNA.
DR RefSeq; NP_001333347.1; NM_001346418.1. [Q86UC2-2]
DR RefSeq; NP_114130.3; NM_031924.5.
DR AlphaFoldDB; Q86UC2; -.
DR SMR; Q86UC2; -.
DR BioGRID; 123776; 8.
DR IntAct; Q86UC2; 8.
DR STRING; 9606.ENSP00000252655; -.
DR iPTMnet; Q86UC2; -.
DR PhosphoSitePlus; Q86UC2; -.
DR BioMuta; RSPH3; -.
DR DMDM; 74750415; -.
DR jPOST; Q86UC2; -.
DR MassIVE; Q86UC2; -.
DR PaxDb; Q86UC2; -.
DR PeptideAtlas; Q86UC2; -.
DR PRIDE; Q86UC2; -.
DR ProteomicsDB; 69797; -. [Q86UC2-1]
DR ProteomicsDB; 69798; -. [Q86UC2-2]
DR DNASU; 83861; -.
DR GeneID; 83861; -.
DR KEGG; hsa:83861; -.
DR UCSC; uc003qrx.4; human. [Q86UC2-1]
DR CTD; 83861; -.
DR DisGeNET; 83861; -.
DR GeneCards; RSPH3; -.
DR GeneReviews; RSPH3; -.
DR HGNC; HGNC:21054; RSPH3.
DR MalaCards; RSPH3; -.
DR MIM; 615876; gene.
DR MIM; 616481; phenotype.
DR neXtProt; NX_Q86UC2; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA162402248; -.
DR VEuPathDB; HostDB:ENSG00000130363; -.
DR eggNOG; ENOG502QQSZ; Eukaryota.
DR InParanoid; Q86UC2; -.
DR OrthoDB; 955313at2759; -.
DR PhylomeDB; Q86UC2; -.
DR TreeFam; TF324184; -.
DR PathwayCommons; Q86UC2; -.
DR SignaLink; Q86UC2; -.
DR SIGNOR; Q86UC2; -.
DR BioGRID-ORCS; 83861; 13 hits in 1044 CRISPR screens.
DR ChiTaRS; RSPH3; human.
DR GeneWiki; RSPH3; -.
DR GenomeRNAi; 83861; -.
DR Pharos; Q86UC2; Tdark.
DR PRO; PR:Q86UC2; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q86UC2; protein.
DR Genevisible; Q86UC2; HS.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR InterPro; IPR009290; Radial_spoke_3.
DR PANTHER; PTHR21648; PTHR21648; 1.
DR Pfam; PF06098; Radial_spoke_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Coiled coil; Cytoplasm;
KW Cytoskeleton; Phosphoprotein; Primary ciliary dyskinesia;
KW Reference proteome.
FT CHAIN 1..560
FT /note="Radial spoke head protein 3 homolog"
FT /id="PRO_0000313741"
FT REGION 134..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 225..249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 526..560
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 215..239
FT /evidence="ECO:0000255"
FT COILED 331..385
FT /evidence="ECO:0000255"
FT COMPBIAS 144..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 286
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:19684019"
FT VAR_SEQ 212..307
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_030128"
FT VARIANT 201
FT /note="N -> S (in dbSNP:rs16889320)"
FT /id="VAR_037720"
FT VARIANT 213
FT /note="R -> Q (in dbSNP:rs34582178)"
FT /id="VAR_037721"
FT VARIANT 398
FT /note="R -> Q (in dbSNP:rs10455840)"
FT /id="VAR_037722"
FT VARIANT 439
FT /note="M -> T (in dbSNP:rs768994)"
FT /id="VAR_037723"
FT VARIANT 484
FT /note="E -> K (in dbSNP:rs12204826)"
FT /id="VAR_037724"
FT VARIANT 518
FT /note="G -> D (in dbSNP:rs3756987)"
FT /id="VAR_037725"
FT CONFLICT 99
FT /note="L -> S (in Ref. 1; BAB71615)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 560 AA; 63687 MW; EEAC4B64D1099019 CRC64;
MTVKPAKAAS LARNLAKRRR TYLGGAAGRS QEPEVPCAAV LPGKPGDRNC PEFPPPDRTL
GCWATDAAPA AGLCGAGSEP SIAPTSCAGN LPSRPPPLLS PLLASRNPCP WHYLHLSGSH
NTLAPTCFKA KLHRKRGSQP PDMASALTDR TSRAPSTYTY TSRPRALPCQ RSRYRDSLTQ
PDEEPMHYGN IMYDRRVIRG NTYALQTGPL LGRPDSLELQ RQREARKRAL ARKQAQEQLR
PQTPEPVEGR KHVDVQTELY LEEIADRIIE VDMECQTDAF LDRPPTPLFI PAKTGKDVAT
QILEGELFDF DLEVKPVLEV LVGKTIEQSL LEVMEEEELA NLRASQREYE ELRNSERAEV
QRLEEQERRH REEKERRKKQ QWEIMHKHNE TSQKIAARAF AQRYLADLLP SVFGSLRDSG
YFYDPIERDI EIGFLPWLMN EVEKTMEYSM VGRTVLDMLI REVVEKRLCM YEHGEDTHQS
PEPEDEPGGP GAMTESLEAS EFLEQSMSQT RELLLDGGYL QRTTYDRRSS QERKFMEERE
LLGQDEETAM RKSLGEEELS
