DRC9_HUMAN
ID DRC9_HUMAN Reviewed; 443 AA.
AC Q9H095; Q9BST2; Q9HAG8;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Dynein regulatory complex protein 9 {ECO:0000250|UniProtKB:A8HQ54};
DE AltName: Full=IQ domain-containing protein G;
GN Name=IQCG; Synonyms=DRC9 {ECO:0000250|UniProtKB:A8HQ54};
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).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 72-443 (ISOFORM 1), AND VARIANT
RP ASP-112.
RC TISSUE=Placenta;
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 X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 389-423 IN COMPLEX WITH CALM,
RP FUNCTION, INTERACTION WITH CALM; HSPA1L AND HSPA8, SUBCELLULAR LOCATION,
RP DOMAIN, AND MUTAGENESIS OF GLN-401.
RX PubMed=24787902; DOI=10.1038/ncomms4811;
RA Chen L.T., Liang W.X., Chen S., Li R.K., Tan J.L., Xu P.F., Luo L.F.,
RA Wang L., Yu S.H., Meng G., Li K.K., Liu T.X., Chen Z., Chen S.J.;
RT "Functional and molecular features of the calmodulin-interacting protein
RT IQCG required for haematopoiesis in zebrafish.";
RL Nat. Commun. 5:3811-3811(2014).
CC -!- FUNCTION: Component of the nexin-dynein regulatory complex (N-DRC), a
CC key regulator of ciliary/flagellar motility which maintains the
CC alignment and integrity of the distal axoneme and regulates microtubule
CC sliding in motile axonemes. Binds calmodulin when cellular Ca(2+)
CC levels are low and thereby contributes to the regulation of calcium and
CC calmodulin-dependent protein kinase IV (CAMK4) activity; contributes to
CC the regulation of CAMK4 signaling cascades. Required for normal axoneme
CC assembly in sperm flagella, normal sperm tail formation and for male
CC fertility. {ECO:0000250|UniProtKB:A3KQH2, ECO:0000250|UniProtKB:A8HQ54,
CC ECO:0000250|UniProtKB:Q80W32}.
CC -!- SUBUNIT: Component of the nexin-dynein regulatory complex (N-DRC) (By
CC similarity). Interacts (via IQ domain) with CALM when calcium levels
CC are low. Does not interact with CALM in the presence of Ca(2+).
CC Interacts with the HSP70 proteins HSPA1L and HSPA8 (PubMed:24787902).
CC May form a complex with CAMK4 and HSP70 (By similarity).
CC {ECO:0000250|UniProtKB:A8HQ54, ECO:0000250|UniProtKB:Q80W32,
CC ECO:0000269|PubMed:24787902}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24787902}. Cell
CC projection, cilium, flagellum {ECO:0000250|UniProtKB:Q80W32}. Cell
CC projection, cilium {ECO:0000250|UniProtKB:Q80W32}. Cytoplasm,
CC cytoskeleton {ECO:0000250|UniProtKB:Q80W32}. Cytoplasm, cytoskeleton,
CC flagellum axoneme {ECO:0000250|UniProtKB:A8HQ54}. Note=First detected
CC in the cytoplasm of pachytene spermatocytes. Colocalizes with alpha-
CC tubulin at the manchette in developing spermatids. Detected in the
CC flagellum of mature testicular spermatozoa, and in the flagellum and
CC post-acrosomal region of the head of epididymal spermatozoa. Detected
CC in cilia in trachea and oviduct. {ECO:0000250|UniProtKB:Q80W32}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H095-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H095-2; Sequence=VSP_024187;
CC -!- DOMAIN: The IQ domain mediates interaction with calmodulin when
CC cellular Ca(2+) levels are low. {ECO:0000269|PubMed:24787902}.
CC -!- SIMILARITY: Belongs to the DRC9 family. {ECO:0000305}.
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DR EMBL; AL136889; CAB66823.1; -; mRNA.
DR EMBL; CR533515; CAG38546.1; -; mRNA.
DR EMBL; AK021729; BAB13881.1; -; mRNA.
DR EMBL; BC004816; AAH04816.2; -; mRNA.
DR CCDS; CCDS3331.1; -. [Q9H095-1]
DR RefSeq; NP_001127907.1; NM_001134435.2. [Q9H095-1]
DR RefSeq; NP_001309956.1; NM_001323027.1. [Q9H095-1]
DR RefSeq; NP_001309957.1; NM_001323028.1.
DR RefSeq; NP_001309958.1; NM_001323029.1. [Q9H095-2]
DR RefSeq; NP_115639.1; NM_032263.4. [Q9H095-1]
DR PDB; 4LZX; X-ray; 1.50 A; B=389-423.
DR PDB; 4M1L; X-ray; 2.10 A; B=376-435.
DR PDBsum; 4LZX; -.
DR PDBsum; 4M1L; -.
DR AlphaFoldDB; Q9H095; -.
DR SMR; Q9H095; -.
DR BioGRID; 123957; 8.
DR IntAct; Q9H095; 4.
DR MINT; Q9H095; -.
DR STRING; 9606.ENSP00000265239; -.
DR iPTMnet; Q9H095; -.
DR PhosphoSitePlus; Q9H095; -.
DR BioMuta; IQCG; -.
DR DMDM; 74752551; -.
DR EPD; Q9H095; -.
DR jPOST; Q9H095; -.
DR MassIVE; Q9H095; -.
DR PaxDb; Q9H095; -.
DR PeptideAtlas; Q9H095; -.
DR PRIDE; Q9H095; -.
DR ProteomicsDB; 80225; -. [Q9H095-1]
DR ProteomicsDB; 80226; -. [Q9H095-2]
DR Antibodypedia; 51727; 75 antibodies from 11 providers.
DR DNASU; 84223; -.
DR Ensembl; ENST00000265239.11; ENSP00000265239.6; ENSG00000114473.14. [Q9H095-1]
DR Ensembl; ENST00000455191.5; ENSP00000407736.1; ENSG00000114473.14. [Q9H095-1]
DR GeneID; 84223; -.
DR KEGG; hsa:84223; -.
DR MANE-Select; ENST00000265239.11; ENSP00000265239.6; NM_032263.5; NP_115639.1.
DR UCSC; uc003fyo.4; human. [Q9H095-1]
DR CTD; 84223; -.
DR DisGeNET; 84223; -.
DR GeneCards; IQCG; -.
DR HGNC; HGNC:25251; IQCG.
DR HPA; ENSG00000114473; Tissue enhanced (fallopian tube, testis).
DR MalaCards; IQCG; -.
DR MIM; 612477; gene.
DR neXtProt; NX_Q9H095; -.
DR OpenTargets; ENSG00000114473; -.
DR PharmGKB; PA134919040; -.
DR VEuPathDB; HostDB:ENSG00000114473; -.
DR eggNOG; ENOG502QQR7; Eukaryota.
DR GeneTree; ENSGT00730000111263; -.
DR HOGENOM; CLU_052522_0_0_1; -.
DR InParanoid; Q9H095; -.
DR OMA; IMNTETL; -.
DR OrthoDB; 1353340at2759; -.
DR PhylomeDB; Q9H095; -.
DR TreeFam; TF326203; -.
DR PathwayCommons; Q9H095; -.
DR SignaLink; Q9H095; -.
DR BioGRID-ORCS; 84223; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; IQCG; human.
DR GenomeRNAi; 84223; -.
DR Pharos; Q9H095; Tbio.
DR PRO; PR:Q9H095; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9H095; protein.
DR Bgee; ENSG00000114473; Expressed in right uterine tube and 146 other tissues.
DR ExpressionAtlas; Q9H095; baseline and differential.
DR Genevisible; Q9H095; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0002177; C:manchette; ISS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB.
DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:UniProtKB.
DR GO; GO:0044782; P:cilium organization; IBA:GO_Central.
DR GO; GO:0007288; P:sperm axoneme assembly; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR042618; IQCG.
DR PANTHER; PTHR14871; PTHR14871; 1.
DR Pfam; PF00612; IQ; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calmodulin-binding; Cell projection;
KW Cilium; Cytoplasm; Cytoskeleton; Differentiation; Flagellum;
KW Reference proteome; Spermatogenesis.
FT CHAIN 1..443
FT /note="Dynein regulatory complex protein 9"
FT /id="PRO_0000282561"
FT DOMAIN 393..422
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..431
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..98
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024187"
FT VARIANT 112
FT /note="A -> D (in dbSNP:rs9880989)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031415"
FT MUTAGEN 401
FT /note="Q->A: Loss of calmodulin binding."
FT /evidence="ECO:0000269|PubMed:24787902"
FT CONFLICT 177
FT /note="D -> H (in Ref. 4; AAH04816)"
FT /evidence="ECO:0000305"
FT HELIX 389..410
FT /evidence="ECO:0007829|PDB:4LZX"
SQ SEQUENCE 443 AA; 51918 MW; F4816EFF3F3386E7 CRC64;
MEEDSLEDSN LPPKVWHSEM TVSVTGEPPS TVEEEGIPKE TDIEIIPEIP ETLEPLSLPD
VLRISAVLED TTDQLSILNY IMPVQYEGRQ SICVKSREMN LEGTNLDKLP MASTITKIPS
PLITEEGPNL PEIRHRGRFA VEFNKMQDLV FKKPTRQTIM TTETLKKIQI DRQFFSDVIA
DTIKELQDSA TYNSLLQALS KERENKMHFY DIIAREEKGR KQIISLQKQL INVKKEWQFE
VQSQNEYIAN LKDQLQEMKA KSNLENRYMK TNTELQIAQT QKKCNRTEEL LVEEIEKLRM
KTEEEARTHT EIEMFLRKEQ QKLEERLEFW MEKYDKDTEM KQNELNALKA TKASDLAHLQ
DLAKMIREYE QVIIEDRIEK ERSKKKVKQD LLELKSVIKL QAWWRGTMIR REIGGFKMPK
DKVDSKDSKG KGKGKDKRRG KKK
