ID RSH4A_HUMAN Reviewed; 716 AA. AC Q5TD94; B4DSI1; Q3KP24; Q5TD95; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 140. DE RecName: Full=Radial spoke head protein 4 homolog A; DE AltName: Full=Radial spoke head-like protein 3; GN Name=RSPH4A; Synonyms=RSHL3; 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 VARIANT PRO-589. RC TISSUE=Brain; 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 MRNA] (ISOFORM 3). 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 IDENTIFICATION, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP VARIANT CILD11 SER-87. RX PubMed=19200523; DOI=10.1016/j.ajhg.2009.01.011; RA Castleman V.H., Romio L., Chodhari R., Hirst R.A., de Castro S.C.P., RA Parker K.A., Ybot-Gonzalez P., Emes R.D., Wilson S.W., Wallis C., RA Johnson C.A., Herrera R.J., Rutman A., Dixon M., Shoemark A., Bush A., RA Hogg C., Gardiner R.M., Reish O., Greene N.D.E., O'Callaghan C., Purton S., RA Chung E.M.K., Mitchison H.M.; RT "Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause RT primary ciliary dyskinesia with central-microtubular-pair abnormalities."; RL Am. J. Hum. Genet. 84:197-209(2009). RN [5] RP INVOLVEMENT IN CILD11. RX PubMed=23798057; DOI=10.1002/humu.22371; RA Daniels M.L., Leigh M.W., Davis S.D., Armstrong M.C., Carson J.L., RA Hazucha M., Dell S.D., Eriksson M., Collins F.S., Knowles M.R., RA Zariwala M.A.; RT "Founder mutation in RSPH4A identified in patients of Hispanic descent with RT Primary Ciliary Dyskinesia."; RL Hum. Mutat. 34:1352-1356(2013). RN [6] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=23993197; DOI=10.1016/j.ajhg.2013.07.013; RA Kott E., Legendre M., Copin B., Papon J.F., Dastot-Le Moal F., RA Montantin G., Duquesnoy P., Piterboth W., Amram D., Bassinet L., RA Beucher J., Beydon N., Deneuville E., Houdouin V., Journel H., Just J., RA Nathan N., Tamalet A., Collot N., Jeanson L., Le Gouez M., Vallette B., RA Vojtek A.M., Epaud R., Coste A., Clement A., Housset B., Louis B., RA Escudier E., Amselem S.; RT "Loss-of-function mutations in RSPH1 cause primary ciliary dyskinesia with RT central-complex and radial-spoke defects."; RL Am. J. Hum. Genet. 93:561-570(2013). RN [7] RP INVOLVEMENT IN CILD11. RX PubMed=25186273; DOI=10.1183/09031936.00052014; RA Raidt J., Wallmeier J., Hjeij R., Onnebrink J.G., Pennekamp P., Loges N.T., RA Olbrich H., Haeffner K., Dougherty G.W., Omran H., Werner C.; RT "Ciliary beat pattern and frequency in genetic variants of primary ciliary RT dyskinesia."; RL Eur. Respir. J. 44:1579-1588(2014). CC -!- FUNCTION: Component of the axonemal radial spoke head which plays an CC important role in ciliary motility (PubMed:19200523). Essential for CC triplet radial spokes (RS1, RS2 and RS3) head assembly in the motile CC cilia (By similarity). {ECO:0000250|UniProtKB:Q8BYM7, CC ECO:0000269|PubMed:19200523}. CC -!- SUBUNIT: Interacts with RSPH6A. {ECO:0000250|UniProtKB:Q8BYM7}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme CC {ECO:0000305}. Cell projection, cilium {ECO:0000269|PubMed:19200523}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q5TD94-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5TD94-2; Sequence=VSP_030125; CC Name=3; CC IsoId=Q5TD94-3; Sequence=VSP_030126, VSP_030127; CC -!- TISSUE SPECIFICITY: Expressed in trachea, lungs, and testes CC (PubMed:23993197). Very strong expression is detected in nasal CC brushings (PubMed:19200523). {ECO:0000269|PubMed:19200523, CC ECO:0000269|PubMed:23993197}. CC -!- DISEASE: Ciliary dyskinesia, primary, 11 (CILD11) [MIM:612649]: 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; reduced fertility CC is often observed in male patients due to abnormalities of sperm tails. CC Half of the patients exhibit situs inversus, due to dysfunction of CC monocilia at the embryonic node and randomization of left-right body CC asymmetry. Primary ciliary dyskinesia associated with situs inversus is CC referred to as Kartagener syndrome. {ECO:0000269|PubMed:19200523, CC ECO:0000269|PubMed:23798057, ECO:0000269|PubMed:25186273}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the flagellar radial spoke RSP4/6 family. CC {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; AK299754; BAG61643.1; -; mRNA. DR EMBL; AL132795; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC106949; AAI06950.1; -; mRNA. DR CCDS; CCDS34521.1; -. [Q5TD94-1] DR CCDS; CCDS55051.1; -. [Q5TD94-3] DR RefSeq; NP_001010892.1; NM_001010892.2. [Q5TD94-1] DR RefSeq; NP_001155136.1; NM_001161664.1. [Q5TD94-3] DR RefSeq; XP_016866315.1; XM_017010826.1. DR PDB; 8J07; EM; 4.10 A; G/H/I/J/g/h/i/j=1-716. DR PDBsum; 8J07; -. DR AlphaFoldDB; Q5TD94; -. DR EMDB; EMD-35888; -. DR SMR; Q5TD94; -. DR BioGRID; 131368; 3. DR ComplexPortal; CPX-8163; Radial spoke complex, ciliiar variant. DR STRING; 9606.ENSP00000229554; -. DR iPTMnet; Q5TD94; -. DR PhosphoSitePlus; Q5TD94; -. DR BioMuta; RSPH4A; -. DR DMDM; 74746178; -. DR jPOST; Q5TD94; -. DR MassIVE; Q5TD94; -. DR PaxDb; 9606-ENSP00000229554; -. DR PeptideAtlas; Q5TD94; -. DR ProteomicsDB; 65005; -. [Q5TD94-1] DR ProteomicsDB; 65006; -. [Q5TD94-2] DR ProteomicsDB; 65007; -. [Q5TD94-3] DR Antibodypedia; 32513; 67 antibodies from 12 providers. DR DNASU; 345895; -. DR Ensembl; ENST00000229554.10; ENSP00000229554.5; ENSG00000111834.13. [Q5TD94-1] DR Ensembl; ENST00000368580.4; ENSP00000357569.4; ENSG00000111834.13. [Q5TD94-2] DR Ensembl; ENST00000368581.8; ENSP00000357570.4; ENSG00000111834.13. [Q5TD94-3] DR GeneID; 345895; -. DR KEGG; hsa:345895; -. DR MANE-Select; ENST00000229554.10; ENSP00000229554.5; NM_001010892.3; NP_001010892.1. DR UCSC; uc003pxe.3; human. [Q5TD94-1] DR AGR; HGNC:21558; -. DR CTD; 345895; -. DR DisGeNET; 345895; -. DR GeneCards; RSPH4A; -. DR GeneReviews; RSPH4A; -. DR HGNC; HGNC:21558; RSPH4A. DR HPA; ENSG00000111834; Group enriched (choroid plexus, fallopian tube). DR MalaCards; RSPH4A; -. DR MIM; 612647; gene. DR MIM; 612649; phenotype. DR neXtProt; NX_Q5TD94; -. DR OpenTargets; ENSG00000111834; -. DR Orphanet; 244; Primary ciliary dyskinesia. DR PharmGKB; PA164725568; -. DR VEuPathDB; HostDB:ENSG00000111834; -. DR eggNOG; ENOG502QSU4; Eukaryota. DR GeneTree; ENSGT00500000044869; -. DR HOGENOM; CLU_021526_1_0_1; -. DR InParanoid; Q5TD94; -. DR OMA; CVYFGNG; -. DR OrthoDB; 131007at2759; -. DR PhylomeDB; Q5TD94; -. DR TreeFam; TF324531; -. DR PathwayCommons; Q5TD94; -. DR BioGRID-ORCS; 345895; 22 hits in 1164 CRISPR screens. DR GeneWiki; RSPH4A; -. DR GenomeRNAi; 345895; -. DR Pharos; Q5TD94; Tbio. DR PRO; PR:Q5TD94; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q5TD94; Protein. DR Bgee; ENSG00000111834; Expressed in right uterine tube and 104 other cell types or tissues. DR GO; GO:0097729; C:9+2 motile cilium; ISS:UniProtKB. DR GO; GO:0005930; C:axoneme; IDA:SYSCILIA_CCNET. DR GO; GO:0005576; C:extracellular region; IEA:GOC. DR GO; GO:0031514; C:motile cilium; IC:BHF-UCL. DR GO; GO:0001534; C:radial spoke; ISS:UniProtKB. DR GO; GO:0001535; C:radial spoke head; ISS:UniProtKB. DR GO; GO:0120336; C:radial spoke head 1; IEA:Ensembl. DR GO; GO:0120337; C:radial spoke head 2; IEA:Ensembl. DR GO; GO:0120338; C:radial spoke head 3; IEA:Ensembl. DR GO; GO:0035082; P:axoneme assembly; IMP:BHF-UCL. DR GO; GO:0003341; P:cilium movement; IMP:BHF-UCL. DR GO; GO:0060294; P:cilium movement involved in cell motility; IEA:InterPro. DR GO; GO:0003351; P:epithelial cilium movement involved in extracellular fluid movement; IEA:Ensembl. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0120221; P:maintenance of ciliary planar beating movement pattern; IEA:Ensembl. DR GO; GO:0062177; P:radial spoke assembly; ISS:UniProtKB. DR CDD; cd22963; DD_CrRSP4-like; 1. DR InterPro; IPR006802; Radial_spoke. DR PANTHER; PTHR13159:SF4; RADIAL SPOKE HEAD PROTEIN 4 HOMOLOG A; 1. DR PANTHER; PTHR13159; RADIAL SPOKEHEAD-RELATED; 1. DR Pfam; PF04712; Radial_spoke; 1. DR Genevisible; Q5TD94; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell projection; Ciliopathy; Cilium; KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Disease variant; KW Kartagener syndrome; Phosphoprotein; Primary ciliary dyskinesia; KW Reference proteome. FT CHAIN 1..716 FT /note="Radial spoke head protein 4 homolog A" FT /id="PRO_0000313738" FT REGION 1..164 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 375..410 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 506..526 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 697..716 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..23 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 50..65 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 80..94 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 142..158 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 375..402 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 700..716 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 396 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BYM7" FT VAR_SEQ 308..554 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_030125" FT VAR_SEQ 555..600 FT /note="GRCNWFNSIQKNEEEEEEEDEEKDDSDYIEQEVGLPLLTPISEDLE -> RF FT RIYPPGQHGYPQISFHNMLLQSFNPTFGLEHMPSPMAKSLKIST (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030126" FT VAR_SEQ 601..716 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030127" FT VARIANT 87 FT /note="P -> S (in CILD11; dbSNP:rs767490154)" FT /evidence="ECO:0000269|PubMed:19200523" FT /id="VAR_055235" FT VARIANT 149 FT /note="T -> S (in dbSNP:rs13213314)" FT /id="VAR_037715" FT VARIANT 464 FT /note="G -> E (in CILD11; uncertain significance; FT dbSNP:rs753041231)" FT /id="VAR_070565" FT VARIANT 556 FT /note="R -> H (in dbSNP:rs6927567)" FT /id="VAR_037716" FT VARIANT 589 FT /note="L -> P (in dbSNP:rs784133)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_037717" FT VARIANT 627 FT /note="N -> H (in dbSNP:rs9488991)" FT /id="VAR_037718" FT VARIANT 700 FT /note="A -> V (in dbSNP:rs9488992)" FT /id="VAR_037719" SQ SEQUENCE 716 AA; 80733 MW; A7951A85FBE6F6E7 CRC64; MEDSTSPKQE KENQEELGET RRPWEGKTAA SPQYSEPESS EPLEAKQGPE TGRQSRSSRP WSPQSRAKTP LGGPAGPETS SPAPVSPREP SSSPSPLAPA RQDLAAPPQS DRTTSVIPEA GTPYPDPLEQ SSDKRESTPH HTSQSEGNTF QQSQQPKPHL CGRRDVSYNN AKQKELRFDV FQEEDSNSDY DLQQPAPGGS EVAPSMLEIT IQNAKAYLLK TSSNSGFNLY DHLSNMLTKI LNERPENAVD IFENISQDVK MAHFSKKFDA LQNENELLPT YEIAEKQKAL FLQGHLEGVD QELEDEIAEN ALPNVMESAF YFEQAGVGLG TDETYRIFLA LKQLTDTHPI QRCRFWGKIL GLEMNYIVAE VEFREGEDEE EVEEEDVAEE RDNGESEAHE DEEDELPKSF YKAPQAIPKE ESRTGANKYV YFVCNEPGRP WVKLPPVIPA QIVIARKIKK FFTGRLDAPI ISYPPFPGNE SNYLRAQIAR ISAGTHVSPL GFYQFGEEEG EEEEEAEGGR NSFEENPDFE GIQVIDLVES LSNWVHHVQH ILSQGRCNWF NSIQKNEEEE EEEDEEKDDS DYIEQEVGLP LLTPISEDLE IQNIPPWTTR LSSNLIPQYA IAVLQSNLWP GAYAFSNGKK FENFYIGWGH KYSPDNYTPP VPPPVYQEYP SGPEITEMDD PSVEEEQAFR AAQEAVLLAA ENEESEEDED EEDDYD //