RSH4A_HUMAN
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 03-AUG-2022, entry version 132.
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 Note=Radial spoke. {ECO:0000305}.
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}.
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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. [Q5TD94-3]
DR AlphaFoldDB; Q5TD94; -.
DR SMR; Q5TD94; -.
DR BioGRID; 131368; 3.
DR STRING; 9606.ENSP00000229554; -.
DR iPTMnet; Q5TD94; -.
DR PhosphoSitePlus; Q5TD94; -.
DR BioMuta; RSPH4A; -.
DR DMDM; 74746178; -.
DR jPOST; Q5TD94; -.
DR MassIVE; Q5TD94; -.
DR PaxDb; Q5TD94; -.
DR PeptideAtlas; Q5TD94; -.
DR PRIDE; Q5TD94; -.
DR ProteomicsDB; 65005; -. [Q5TD94-1]
DR ProteomicsDB; 65006; -. [Q5TD94-2]
DR ProteomicsDB; 65007; -. [Q5TD94-3]
DR Antibodypedia; 32513; 56 antibodies from 11 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 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; AQFQKKM; -.
DR PhylomeDB; Q5TD94; -.
DR TreeFam; TF324531; -.
DR PathwayCommons; Q5TD94; -.
DR BioGRID-ORCS; 345895; 22 hits in 1086 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 102 other tissues.
DR Genevisible; Q5TD94; HS.
DR GO; GO:0005930; C:axoneme; IDA:SYSCILIA_CCNET.
DR GO; GO:0031514; C:motile cilium; IC:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0001534; C:radial spoke; ISS:UniProtKB.
DR GO; GO:0001535; C:radial spoke head; 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:0120221; P:maintenance of ciliary planar beating movement pattern; IEA:Ensembl.
DR GO; GO:0062177; P:radial spoke assembly; ISS:UniProtKB.
DR InterPro; IPR006802; Radial_spoke.
DR PANTHER; PTHR13159; PTHR13159; 1.
DR Pfam; PF04712; Radial_spoke; 1.
PE 1: Evidence at protein level;
KW 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; unknown pathological
FT significance; 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
