Q8NEP3 (DAAF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dynein assembly factor 1, axonemal

Alternative name(s):
Leucine-rich repeat-containing protein 50

Gene names

Name:	DNAAF1
Synonyms:	LRRC50

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	725 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cilium-specific protein required for the stability of the ciliary architecture. Plays a role in cytoplasmic preassembly of dynein arms. Involved in regulation of microtubule-based cilia and actin-based brush border microvilli. Ref.5 Ref.6 Ref.7
Subcellular location	Cell projection › cilium. Cytoplasm. Cytoplasm › cytoskeleton › spindle pole. Note: In HEK293T cells, it is diffusely cytoplasmic and concentrates at the mitotic spindle poles, while in MDCK cells, it localizes in the cilium. In vivo, this protein is probably restricted to the cilium. Ref.5
Tissue specificity	Mainly expressed in trachea and testis. Ref.7
Involvement in disease	Primary ciliary dyskinesia 13 (CILD13) [MIM:613193]: A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. At ultrastructural level, CILD13 is characterized by a marked reduction or absence of both dynein arms from the patients cilia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7
Sequence similarities	Belongs to the DNAAF1 family. Contains 6 LRR (leucine-rich) repeats. Contains 1 LRRCT domain.
Sequence caution	The sequence BAB71645.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell projection Cilium Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Ciliopathy Disease mutation Primary ciliary dyskinesia
Domain	Leucine-rich repeat Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	determination of digestive tract left/right asymmetry Inferred from mutant phenotype Ref.7. Source: BHF-UCL determination of liver left/right asymmetry Inferred from mutant phenotype Ref.7. Source: BHF-UCL determination of pancreatic left/right asymmetry Inferred from mutant phenotype Ref.7. Source: BHF-UCL epithelial cilium movement involved in determination of left/right asymmetry Inferred by curator Ref.7. Source: BHF-UCL heart looping Inferred from mutant phenotype Ref.6Ref.7. Source: BHF-UCL inner dynein arm assembly Inferred from mutant phenotype Ref.6. Source: BHF-UCL left/right pattern formation Inferred from mutant phenotype Ref.6. Source: BHF-UCL lung development Inferred from mutant phenotype Ref.7. Source: BHF-UCL motile cilium assembly Inferred from mutant phenotype Ref.7. Source: BHF-UCL outer dynein arm assembly Inferred from mutant phenotype Ref.6. Source: BHF-UCL regulation of cilium beat frequency Inferred from mutant phenotype Ref.6. Source: BHF-UCL
Cellular_component	cilium axoneme Inferred from direct assay Ref.5. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA spindle pole Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	dynein binding Inferred from mutant phenotype Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8NEP3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8NEP3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-252: Missing.
     343-343: R → RGMRSAEDNSPRVPLRL

Note: No experimental confirmation available.

Isoform 3 (identifier: Q8NEP3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     409-725: GPEPEGTLPA...LTAFPAPKAS → DPATVTACEG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 725	725	Dynein assembly factor 1, axonemal		PRO_0000232889
Regions
	Repeat	107 – 129	23	LRR 1
	Repeat	130 – 151	22	LRR 2
	Repeat	152 – 173	22	LRR 3
	Repeat	174 – 195	22	LRR 4
	Repeat	196 – 217	22	LRR 5
	Repeat	221 – 242	22	LRR 6
	Domain	256 – 294	39	LRRCT
	Compositional bias	391 – 513	123	Pro-rich
Natural variations
	Alternative sequence	1 – 252	252	Missing in isoform 2.		VSP_036354
	Alternative sequence	343	1	R → RGMRSAEDNSPRVPLRL in isoform 2.		VSP_036355
	Alternative sequence	409 – 725	317	GPEPE…APKAS → DPATVTACEG in isoform 3.		VSP_036356
	Natural variant	42 – 117	76	Missing in CILD13.		VAR_063097
	Natural variant	175	1	L → R in CILD13. Ref.7		VAR_063098
	Natural variant	387	1	D → E. Corresponds to variant rs36062234 [ dbSNP | Ensembl ].		VAR_047662
	Natural variant	393	1	K → R. Ref.1 Ref.3 Ref.4 Corresponds to variant rs17856705 [ dbSNP | Ensembl ].		VAR_047663
	Natural variant	432	1	E → D. Corresponds to variant rs9972733 [ dbSNP | Ensembl ].		VAR_047664
	Natural variant	502	1	P → L. Ref.1 Ref.3 Ref.4 Corresponds to variant rs11644164 [ dbSNP | Ensembl ].		VAR_047665
	Natural variant	545	1	F → C. Ref.3 Corresponds to variant rs17856706 [ dbSNP | Ensembl ].		VAR_047666
	Natural variant	633	1	L → S. Ref.1 Ref.3 Corresponds to variant rs2288020 [ dbSNP | Ensembl ].		VAR_047667
	Natural variant	659	1	L → P. Ref.1 Ref.3 Corresponds to variant rs2288022 [ dbSNP | Ensembl ].		VAR_047668
	Natural variant	659	1	L → V. Corresponds to variant rs2288021 [ dbSNP | Ensembl ].		VAR_047669
	Natural variant	675	1	S → T. Ref.1 Ref.3 Corresponds to variant rs2288023 [ dbSNP | Ensembl ].		VAR_047670
	Natural variant	703	1	G → R. Corresponds to variant rs4150188 [ dbSNP | Ensembl ].		VAR_047671
	Natural variant	712	1	P → A. Corresponds to variant rs4150187 [ dbSNP | Ensembl ].		VAR_047672
Experimental info
	Sequence conflict	307	1	Q → E in CAH10390. Ref.4
	Sequence conflict	366	1	P → L in CAH10394. Ref.4
	Sequence conflict	457	1	G → R in BAG58765. Ref.2
	Sequence conflict	485	1	D → G in CAH10394. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 5. Checksum: CFDBF86796FA61B0	FASTA	725	80,026
	10 20 30 40 50 60 MHPEPSEPAT GGAAELDCAQ EPGVEESAGD HGSAGRGGCK EEINDPKEIC VGSSDTSYHS 70 80 90 100 110 120 QQKQSGDNGS GGHFAHPRED REDRGPRMTK SSLQKLCKQH KLYITPALND TLYLHFKGFD 130 140 150 160 170 180 RIENLEEYTG LRCLWLQSNG IQKIENLEAQ TELRCLFLQM NLLRKIENLE PLQKLDALNL 190 200 210 220 230 240 SNNYIKTIEN LSCLPVLNTL QMAHNHLETV EDIQHLQECL RLCVLDLSHN KLSDPEILSI 250 260 270 280 290 300 LESMPDLRVL NLMGNPVIRQ IPNYRRTVTV RLKHLTYLDD RPVFPKDRAC AEAWARGGYA 310 320 330 340 350 360 AEKEERQQWE SRERKKITDS IEALAMIKQR AEERKRQRES QERGEMTSSD DGENVPASAE 370 380 390 400 410 420 GKEEPPGDRE TRQKMELFVK ESFEAKDELC PEKPSGEEPP VEAKREDGGP EPEGTLPAET 430 440 450 460 470 480 LLLSSPVEVK GEDGDGEPEG TLPAEAPPPP PPVEVKGEDG DQEPEGTLPA ETLLLSPPVK 490 500 510 520 530 540 VKGEDGDREP EGTLPAEAPP PPPLGAAREE PTPQAVATEG VFVTELDGTR TEDLETIRLE 550 560 570 580 590 600 TKETFCIDDL PDLEDDDETG KSLEDQNMCF PKIEVISSLS DDSDPELDYT SLPVLENLPT 610 620 630 640 650 660 DTLSNIFAVS KDTSKAARVP FTDIFKKEAK RDLEIRKQDT KSPRPLIQEL SDEDPSGQLL 670 680 690 700 710 720 MPPTCQRDAA PLTSSGDRDS DFLAASSPVP TESAATPPET CVGVAQPSQA LPTWDLTAFP APKAS
	Isoform 2 [UniParc]. Checksum: 5661910591E86359	FASTA	489	53,531
	10 20 30 40 50 60 MGNPVIRQIP NYRRTVTVRL KHLTYLDDRP VFPKDRACAE AWARGGYAAE KEERQQWESR 70 80 90 100 110 120 ERKKITDSIE ALAMIKQRAE ERKRQRESQE RGMRSAEDNS PRVPLRLGEM TSSDDGENVP 130 140 150 160 170 180 ASAEGKEEPP GDRETRQKME LFVKESFEAK DELCPEKPSG EEPPVEAKRE DGGPEPEGTL 190 200 210 220 230 240 PAETLLLSSP VEVKGEDGDG EPEGTLPAEA PPPPPPVEVK GEDGDQEPEG TLPAETLLLS 250 260 270 280 290 300 PPVKVKGEDG DREPEGTLPA EAPPPPPLGA AREEPTPQAV ATEGVFVTEL DGTRTEDLET 310 320 330 340 350 360 IRLETKETFC IDDLPDLEDD DETGKSLEDQ NMCFPKIEVI SSLSDDSDPE LDYTSLPVLE 370 380 390 400 410 420 NLPTDTLSNI FAVSKDTSKA ARVPFTDIFK KEAKRDLEIR KQDTKSPRPL IQELSDEDPS 430 440 450 460 470 480 GQLLMPPTCQ RDAAPLTSSG DRDSDFLAAS SPVPTESAAT PPETCVGVAQ PSQALPTWDL TAFPAPKAS
	Isoform 3 [UniParc]. Checksum: 2BF7BA4C8CE55708	FASTA	418	47,267
	10 20 30 40 50 60 MHPEPSEPAT GGAAELDCAQ EPGVEESAGD HGSAGRGGCK EEINDPKEIC VGSSDTSYHS 70 80 90 100 110 120 QQKQSGDNGS GGHFAHPRED REDRGPRMTK SSLQKLCKQH KLYITPALND TLYLHFKGFD 130 140 150 160 170 180 RIENLEEYTG LRCLWLQSNG IQKIENLEAQ TELRCLFLQM NLLRKIENLE PLQKLDALNL 190 200 210 220 230 240 SNNYIKTIEN LSCLPVLNTL QMAHNHLETV EDIQHLQECL RLCVLDLSHN KLSDPEILSI 250 260 270 280 290 300 LESMPDLRVL NLMGNPVIRQ IPNYRRTVTV RLKHLTYLDD RPVFPKDRAC AEAWARGGYA 310 320 330 340 350 360 AEKEERQQWE SRERKKITDS IEALAMIKQR AEERKRQRES QERGEMTSSD DGENVPASAE 370 380 390 400 410 GKEEPPGDRE TRQKMELFVK ESFEAKDELC PEKPSGEEPP VEAKREDGDP ATVTACEG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANTS ARG-393; LEU-502; SER-633; PRO-659 AND THR-675. Tissue: Subthalamic nucleus and Testis.
[2]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ARG-393; LEU-502; CYS-545; SER-633; PRO-659 AND THR-675. Tissue: Testis.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-548 AND 567-725 (ISOFORM 1), VARIANTS ARG-393 AND LEU-502. Tissue: Testis.
[5]	"LRRC50, a conserved ciliary protein implicated in polycystic kidney disease." van Rooijen E., Giles R.H., Voest E.E., van Rooijen C., Schulte-Merker S., van Eeden F.J. J. Am. Soc. Nephrol. 19:1128-1138(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects." Loges N.T., Olbrich H., Becker-Heck A., Haffner K., Heer A., Reinhard C., Schmidts M., Kispert A., Zariwala M.A., Leigh M.W., Knowles M.R., Zentgraf H., Seithe H., Nurnberg G., Nurnberg P., Reinhardt R., Omran H. Am. J. Hum. Genet. 85:883-889(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INVOLVEMENT IN CILD13.
[7]	"Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia." Duquesnoy P., Escudier E., Vincensini L., Freshour J., Bridoux A.M., Coste A., Deschildre A., de Blic J., Legendre M., Montantin G., Tenreiro H., Vojtek A.M., Loussert C., Clement A., Escalier D., Bastin P., Mitchell D.R., Amselem S. Am. J. Hum. Genet. 85:890-896(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, VARIANTS CILD13 42-GLU--LYS-117 DEL AND ARG-175.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK057238 mRNA. Translation: BAB71392.1. AK058059 mRNA. Translation: BAB71645.1. Different initiation. AK295990 mRNA. Translation: BAG58765.1. AC009123 Genomic DNA. No translation available. AC040169 Genomic DNA. No translation available. BC024009 mRNA. Translation: AAH24009.3. AL137334 mRNA. Translation: CAH10706.1. AL833328 mRNA. Translation: CAH10390.1. AL833336 mRNA. Translation: CAH10394.1.
IPI	IPI00065458. IPI00549355. IPI00921305.
RefSeq	NP_848547.4. NM_178452.4.
UniGene	Hs.310164.
3D structure databases
ProteinModelPortal	Q8NEP3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000367815.
PTM databases
PhosphoSite	Q8NEP3.
Polymorphism databases
DMDM	215274261.
Proteomic databases
PaxDb	Q8NEP3.
PRIDE	Q8NEP3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334315; ENSP00000334593; ENSG00000154099. ENST00000378553; ENSP00000367815; ENSG00000154099. ENST00000563093; ENSP00000457373; ENSG00000154099.
GeneID	123872.
KEGG	hsa:123872.
UCSC	uc002fhl.4. human. uc010vnw.2. human.
Organism-specific databases
CTD	123872.
GeneCards	GC16P084179.
H-InvDB	HIX0013289.
HGNC	HGNC:30539. DNAAF1.
HPA	HPA041166.
MIM	613190. gene. 613193. phenotype.
neXtProt	NX_Q8NEP3.
Orphanet	244. Primary ciliary dyskinesia.
PharmGKB	PA142671510.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOVERGEN	HBG066969.
InParanoid	Q8NEP3.
OMA	MAHNHLE.
OrthoDB	EOG4FTW04.
Gene expression databases
ArrayExpress	Q8NEP3.
Bgee	Q8NEP3.
CleanEx	HS_LRRC50.
Genevestigator	Q8NEP3.
GermOnline	ENSG00000154099. Homo sapiens.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. [Graphical view]
PROSITE	PS51450. LRR. 6 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	123872.
NextBio	81173.
SOURCE	Search...

Entry information

Entry name

DAAF1_HUMAN

Accession

Primary (citable) accession number: Q8NEP3
Secondary accession number(s): B4DJA3 , Q69YI8, Q69YJ0, Q69YW5, Q96LP3, Q96MB6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2006
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 93 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.