CF276_HUMAN
ID CF276_HUMAN Reviewed; 169 AA.
AC Q5T5A4; Q5T5A3;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Cilia- and flagella-associated protein 276 {ECO:0000312|HGNC:HGNC:32331};
GN Name=CFAP276 {ECO:0000312|HGNC:HGNC:32331};
GN Synonyms=C1orf194 {ECO:0000312|HGNC:HGNC:32331};
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 2).
RX PubMed=8889548; DOI=10.1101/gr.6.9.791;
RA Bonaldo M.F., Lennon G., Soares M.B.;
RT "Normalization and subtraction: two approaches to facilitate gene
RT discovery.";
RL Genome Res. 6:791-806(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP SUBCELLULAR LOCATION, VARIANTS ILE-28 AND ASN-122, TISSUE SPECIFICITY,
RP CHARACTERIZATION OF VARIANTS ILE-28 AND ASN-122, FUNCTION, AND INVOLVEMENT
RP IN CHAROT-MARIE-TOOTH DISEASE.
RX PubMed=31199454; DOI=10.1093/brain/awz151;
RA Sun S.C., Ma D., Li M.Y., Zhang R.X., Huang C., Huang H.J., Xie Y.Z.,
RA Wang Z.J., Liu J., Cai D.C., Liu C.X., Yang Q., Bao F.X., Gong X.L.,
RA Li J.R., Hui Z., Wei X.F., Zhong J.M., Zhou W.J., Shang X., Zhang C.,
RA Liu X.G., Tang B.S., Xiong F., Xu X.M.;
RT "Mutations in C1orf194, encoding a calcium regulator, cause dominant
RT Charcot-Marie-Tooth disease.";
RL Brain 142:2215-2229(2019).
CC -!- FUNCTION: Microtubule inner protein (MIP) part of the dynein-decorated
CC doublet microtubules (DMTs) in cilia axoneme, which is required for
CC motile cilia beating (By similarity). May play an important role for
CC the maintenance of myelin-axon integrity (By similarity). May affect
CC intracellular Ca(2+) homeostasis (PubMed:31199454).
CC {ECO:0000250|UniProtKB:E1B9I5, ECO:0000250|UniProtKB:Q9DAD0,
CC ECO:0000269|PubMed:31199454}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31199454}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:31199454}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000250|UniProtKB:E1B9I5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5T5A4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5T5A4-2; Sequence=VSP_027993;
CC -!- TISSUE SPECIFICITY: Expressed in cerebrum, cerebellum, gastrocnemius
CC muscle, spinal cord and lung tissues. {ECO:0000269|PubMed:31199454}.
CC -!- DISEASE: Note=CFAP276 mutations may be the cause of Charcot-Marie-Tooth
CC disease, a disorder of the peripheral nervous system, characterized by
CC progressive weakness and atrophy, initially of the peroneal muscles and
CC later of the distal muscles of the arms. Charcot-Marie-Tooth disease is
CC classified in two main groups on the basis of electrophysiologic
CC properties and histopathology: primary peripheral demyelinating
CC neuropathies (designated CMT1 when they are dominantly inherited) and
CC primary peripheral axonal neuropathies (CMT2). Demyelinating
CC neuropathies are characterized by severely reduced nerve conduction
CC velocities (less than 38 m/sec), segmental demyelination and
CC remyelination with onion bulb formations on nerve biopsy, slowly
CC progressive distal muscle atrophy and weakness, absent deep tendon
CC reflexes, and hollow feet. Intermediate forms of Charcot-Marie-Tooth
CC disease exist and are characterized by clinical and pathologic features
CC intermediate between demyelinating and axonal peripheral neuropathies,
CC and motor median nerve conduction velocities ranging from 25 to 45
CC m/sec. {ECO:0000269|PubMed:31199454}.
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DR EMBL; BM726900; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL356488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS41364.1; -. [Q5T5A4-2]
DR RefSeq; NP_001116433.1; NM_001122961.1. [Q5T5A4-2]
DR AlphaFoldDB; Q5T5A4; -.
DR BioGRID; 126029; 1.
DR STRING; 9606.ENSP00000358965; -.
DR iPTMnet; Q5T5A4; -.
DR PhosphoSitePlus; Q5T5A4; -.
DR BioMuta; C1orf194; -.
DR DMDM; 74745049; -.
DR MassIVE; Q5T5A4; -.
DR PeptideAtlas; Q5T5A4; -.
DR PRIDE; Q5T5A4; -.
DR Antibodypedia; 33746; 46 antibodies from 9 providers.
DR DNASU; 127003; -.
DR Ensembl; ENST00000369948.8; ENSP00000358964.3; ENSG00000179902.13. [Q5T5A4-1]
DR Ensembl; ENST00000369949.8; ENSP00000358965.4; ENSG00000179902.13. [Q5T5A4-2]
DR GeneID; 127003; -.
DR KEGG; hsa:127003; -.
DR MANE-Select; ENST00000369948.8; ENSP00000358964.3; NM_001245025.3; NP_001231954.1.
DR UCSC; uc009wev.4; human. [Q5T5A4-1]
DR CTD; 127003; -.
DR DisGeNET; 127003; -.
DR GeneCards; C1orf194; -.
DR HGNC; HGNC:32331; CFAP276.
DR HPA; ENSG00000179902; Group enriched (fallopian tube, testis).
DR MIM; 618682; gene.
DR neXtProt; NX_Q5T5A4; -.
DR OpenTargets; ENSG00000179902; -.
DR VEuPathDB; HostDB:ENSG00000179902; -.
DR eggNOG; ENOG502S2J1; Eukaryota.
DR GeneTree; ENSGT01030000234625; -.
DR HOGENOM; CLU_133894_0_0_1; -.
DR InParanoid; Q5T5A4; -.
DR OMA; ANIRQWI; -.
DR OrthoDB; 1429280at2759; -.
DR PhylomeDB; Q5T5A4; -.
DR TreeFam; TF325898; -.
DR PathwayCommons; Q5T5A4; -.
DR BioGRID-ORCS; 127003; 10 hits in 1033 CRISPR screens.
DR GenomeRNAi; 127003; -.
DR Pharos; Q5T5A4; Tdark.
DR PRO; PR:Q5T5A4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T5A4; protein.
DR Bgee; ENSG00000179902; Expressed in right uterine tube and 115 other tissues.
DR ExpressionAtlas; Q5T5A4; baseline and differential.
DR Genevisible; Q5T5A4; HS.
DR GO; GO:0005879; C:axonemal microtubule; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0015232; F:heme transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0097037; P:heme export; IBA:GO_Central.
DR InterPro; IPR022179; DUF3695.
DR Pfam; PF12494; DUF3695; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Charcot-Marie-Tooth disease;
KW Cytoplasm; Cytoskeleton; Disease variant; Neurodegeneration; Neuropathy;
KW Reference proteome.
FT CHAIN 1..169
FT /note="Cilia- and flagella-associated protein 276"
FT /id="PRO_0000303065"
FT REGION 26..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..27
FT /note="MPPTRDPFQQPTLDNDDSYLGELRASK -> MERSPSRRRRLEEAP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:8889548"
FT /id="VSP_027993"
FT VARIANT 28
FT /note="K -> I (found in patients with an intermediate form
FT of Charcot-Marie-Tooth disease; does not affect subcellular
FT location; reduced protein expression; increased
FT intracellular Ca(2+); dbSNP:rs1553246861)"
FT /evidence="ECO:0000269|PubMed:31199454"
FT /id="VAR_082033"
FT VARIANT 122
FT /note="I -> N (probable disease-associated variant found in
FT patients with a form of Charcot-Marie-Tooth disease leading
FT to demyelinating form; does not affect subcellular
FT location; increased protein expression; increased
FT aggregation in vesicles; increased intracellular Ca(2+);
FT decreased mitochondrial Ca(2+); dbSNP:rs1553246716)"
FT /evidence="ECO:0000269|PubMed:31199454"
FT /id="VAR_082034"
SQ SEQUENCE 169 AA; 19350 MW; 5C8CA2A4D440519B CRC64;
MPPTRDPFQQ PTLDNDDSYL GELRASKKLP YKNPTHLAQQ QEPWSRLNST PTITSMRRDA
YYFDPEIPKD DLDFRLAALY NHHTGTFKNK SEILLNQKTT QDTYRTKIQF PGEFLTPPTP
PITFLANIRH WINPKKESIH SIQGSIVSPH TAATNGGYSR KKDGGFFST
