ID EFHB_HUMAN Reviewed; 833 AA. AC Q8N7U6; A6ND25; A8MPR3; Q6ZWK9; Q8IV58; Q96LQ6; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 4. DT 02-OCT-2024, entry version 146. DE RecName: Full=EF-hand domain-containing family member B {ECO:0000305}; DE AltName: Full=Cilia- and flagella-associated protein 21; GN Name=EFHB {ECO:0000312|HGNC:HGNC:26330}; Synonyms=CFAP21; 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] (ISOFORMS 2 AND 3), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 598-833 (ISOFORM 1), AND VARIANT ILE-331. RC TISSUE=Kidney proximal tubule, Lung, and Testis; 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=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-331 RP AND ILE-382. RC TISSUE=Lung; 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 FUNCTION, INTERACTION WITH ORAI1 AND STIM1, AND SUBCELLULAR LOCATION. RX PubMed=30481768; DOI=10.1159/000495494; RA Albarran L., Lopez J.J., Jardin I., Sanchez-Collado J., Berna-Erro A., RA Smani T., Camello P.J., Salido G.M., Rosado J.A.; RT "EFHB is a Novel Cytosolic Ca2+ Sensor That Modulates STIM1-SARAF RT Interaction."; RL Cell. Physiol. Biochem. 51:1164-1178(2018). RN [6] {ECO:0007744|PDB:7UNG} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS), FUNCTION, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=36191189; DOI=10.1073/pnas.2207605119; RA Gui M., Croft J.T., Zabeo D., Acharya V., Kollman J.M., Burgoyne T., RA Hoog J.L., Brown A.; RT "SPACA9 is a lumenal protein of human ciliary singlet and doublet RT microtubules."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2207605119-e2207605119(2022). 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 (PubMed:36191189). Cytosolic sensor for calcium, CC modulates the interaction of STIM1 and ORAI1 upon store depletion and CC the activation of store-operated Ca(2+) entry (SOCE) and NFAT CC translocation from cytosol to nucleus (PubMed:30481768). CC {ECO:0000269|PubMed:30481768, ECO:0000269|PubMed:36191189}. CC -!- SUBUNIT: Microtubule inner protein component of sperm flagellar doublet CC microtubules (By similarity). Interacts with STIM1 and ORAI1; the CC interactions take place upon Ca(2+)-store depletion and dissociate CC through a Ca(2+)-dependent mechanism. Interaction with STIM1 inhibits CC STIM1 interaction with SARAF (PubMed:30481768). CC {ECO:0000250|UniProtKB:Q8CDU5, ECO:0000269|PubMed:30481768}. CC -!- INTERACTION: CC Q8N7U6; Q96D31: ORAI1; NbExp=2; IntAct=EBI-25602059, EBI-2291476; CC Q8N7U6; Q13586: STIM1; NbExp=3; IntAct=EBI-25602059, EBI-448878; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme CC {ECO:0000269|PubMed:36191189}. Cytoplasm, cytoskeleton, flagellum CC axoneme {ECO:0000250|UniProtKB:Q8CDU5}. Cytoplasm CC {ECO:0000305|PubMed:30481768}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N7U6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N7U6-2; Sequence=VSP_020864, VSP_020865; CC Name=3; CC IsoId=Q8N7U6-3; Sequence=VSP_020862, VSP_020863; CC -!- TISSUE SPECIFICITY: Expressed in airway epithelial cells. CC {ECO:0000269|PubMed:36191189}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH28198.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB71614.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AK057929; BAB71614.1; ALT_INIT; mRNA. DR EMBL; AK097644; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK122616; BAC85491.1; -; mRNA. DR EMBL; AC104182; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471055; EAW64300.1; -; Genomic_DNA. DR EMBL; BC028198; AAH28198.1; ALT_INIT; mRNA. DR CCDS; CCDS33715.2; -. [Q8N7U6-1] DR CCDS; CCDS82744.1; -. [Q8N7U6-3] DR RefSeq; NP_001317617.1; NM_001330688.1. [Q8N7U6-3] DR RefSeq; NP_653316.3; NM_144715.3. [Q8N7U6-1] DR PDB; 7UNG; EM; 3.60 A; 1/2=1-833. DR PDB; 8J07; EM; 4.10 A; 1A/1B/1C=1-833. DR PDBsum; 7UNG; -. DR PDBsum; 8J07; -. DR AlphaFoldDB; Q8N7U6; -. DR EMDB; EMD-26624; -. DR EMDB; EMD-35888; -. DR SMR; Q8N7U6; -. DR BioGRID; 127397; 2. DR IntAct; Q8N7U6; 3. DR STRING; 9606.ENSP00000295824; -. DR iPTMnet; Q8N7U6; -. DR PhosphoSitePlus; Q8N7U6; -. DR BioMuta; EFHB; -. DR DMDM; 313104304; -. DR MassIVE; Q8N7U6; -. DR PaxDb; 9606-ENSP00000295824; -. DR PeptideAtlas; Q8N7U6; -. DR ProteomicsDB; 72328; -. [Q8N7U6-1] DR ProteomicsDB; 72329; -. [Q8N7U6-2] DR ProteomicsDB; 72330; -. [Q8N7U6-3] DR Antibodypedia; 27043; 113 antibodies from 17 providers. DR DNASU; 151651; -. DR Ensembl; ENST00000295824.14; ENSP00000295824.9; ENSG00000163576.18. [Q8N7U6-1] DR Ensembl; ENST00000344838.8; ENSP00000342263.4; ENSG00000163576.18. [Q8N7U6-3] DR GeneID; 151651; -. DR KEGG; hsa:151651; -. DR MANE-Select; ENST00000295824.14; ENSP00000295824.9; NM_144715.4; NP_653316.3. DR UCSC; uc003cbl.5; human. [Q8N7U6-1] DR AGR; HGNC:26330; -. DR CTD; 151651; -. DR DisGeNET; 151651; -. DR GeneCards; EFHB; -. DR HGNC; HGNC:26330; EFHB. DR HPA; ENSG00000163576; Tissue enhanced (fallopian tube, testis). DR neXtProt; NX_Q8N7U6; -. DR OpenTargets; ENSG00000163576; -. DR PharmGKB; PA134987079; -. DR VEuPathDB; HostDB:ENSG00000163576; -. DR eggNOG; KOG0032; Eukaryota. DR GeneTree; ENSGT00530000063528; -. DR HOGENOM; CLU_017580_0_0_1; -. DR InParanoid; Q8N7U6; -. DR OMA; YGMETPH; -. DR OrthoDB; 317740at2759; -. DR PhylomeDB; Q8N7U6; -. DR TreeFam; TF323832; -. DR PathwayCommons; Q8N7U6; -. DR SignaLink; Q8N7U6; -. DR BioGRID-ORCS; 151651; 13 hits in 1148 CRISPR screens. DR ChiTaRS; EFHB; human. DR GenomeRNAi; 151651; -. DR Pharos; Q8N7U6; Tdark. DR PRO; PR:Q8N7U6; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q8N7U6; protein. DR Bgee; ENSG00000163576; Expressed in bronchial epithelial cell and 106 other cell types or tissues. DR ExpressionAtlas; Q8N7U6; baseline and differential. DR GO; GO:0160111; C:axonemal A tubule inner sheath; ISS:UniProtKB. DR GO; GO:0005879; C:axonemal microtubule; IDA:UniProtKB. DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0061891; F:calcium ion sensor activity; IMP:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IEA:UniProtKB-KW. DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB. DR GO; GO:0032091; P:negative regulation of protein binding; IMP:UniProtKB. DR GO; GO:0070884; P:regulation of calcineurin-NFAT signaling cascade; IMP:UniProtKB. DR GO; GO:2001256; P:regulation of store-operated calcium entry; IMP:UniProtKB. DR CDD; cd00051; EFh; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR040193; EFHC1/EFHC2/EFHB. DR PANTHER; PTHR12086; EF-HAND DOMAIN C-TERMINAL CONTAINING PROTEIN; 1. DR PANTHER; PTHR12086:SF12; EF-HAND DOMAIN-CONTAINING FAMILY MEMBER B; 1. DR Pfam; PF13499; EF-hand_7; 1. DR SMART; SM00054; EFh; 2. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Calcium transport; KW Cell projection; Cilium; Cytoplasm; Cytoskeleton; Flagellum; Ion transport; KW Metal-binding; Proteomics identification; Reference proteome; Repeat; KW Transport. FT CHAIN 1..833 FT /note="EF-hand domain-containing family member B" FT /id="PRO_0000252094" FT DOMAIN 561..596 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 597..632 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 574 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305" FT BINDING 578 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305" FT BINDING 580 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305" FT BINDING 585 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000305" FT BINDING 610 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 612 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 614 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 621 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT VAR_SEQ 1..130 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020862" FT VAR_SEQ 131..183 FT /note="GRVCGSSQAAGSRRAPLASGPEGVEELVGKPAFVMEPRQEMEKESTCVLMKP FT N -> MMAHCRIDLLGSSDPPTSASQIAETTDVSHHAGLIEFLALSNSSALASRSVEI FT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020863" FT VAR_SEQ 576..632 FT /note="KGDGMIDKDELQEACDQANLSLDDKLLDQLFDYCDVDNDGFINYLEFANFLN FT WKDKM -> AGVQWRDLGSLQPPPPRFKRFSCLSLPSSWDYRHLPPHPNFRIFSRDGVS FT PCWPGWS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020864" FT VAR_SEQ 633..833 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020865" FT VARIANT 99 FT /note="G -> V (in dbSNP:rs17795400)" FT /id="VAR_055296" FT VARIANT 269 FT /note="P -> S (in dbSNP:rs13078867)" FT /id="VAR_055297" FT VARIANT 331 FT /note="V -> I (in dbSNP:rs2931403)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_027750" FT VARIANT 382 FT /note="T -> I (in dbSNP:rs2929366)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027751" FT VARIANT 663 FT /note="Q -> P (in dbSNP:rs9868950)" FT /id="VAR_027752" FT VARIANT 826 FT /note="R -> W (in dbSNP:rs11917204)" FT /id="VAR_055298" FT CONFLICT 1 FT /note="M -> V (in Ref. 1; AK097644)" FT /evidence="ECO:0000305" FT CONFLICT 276 FT /note="T -> S (in Ref. 1; BAC85491)" FT /evidence="ECO:0000305" FT CONFLICT 492 FT /note="Q -> R (in Ref. 1; AK097644)" FT /evidence="ECO:0000305" FT CONFLICT 628 FT /note="W -> C (in Ref. 1; BAC85491)" FT /evidence="ECO:0000305" FT CONFLICT 685 FT /note="R -> W (in Ref. 1; BAC85491)" FT /evidence="ECO:0000305" FT CONFLICT 737 FT /note="I -> T (in Ref. 1; BAC85491)" FT /evidence="ECO:0000305" SQ SEQUENCE 833 AA; 93802 MW; 52764E07C4767F15 CRC64; MNMEIGHPHE GKDDLGDKRV IMGTKFPMEL GIRVGLGKED SRCGESPVVS NKCEGRMAPP ETKFPLSKGL EMGLERQNIS RTVMQRGSLG VDSVSASQGT KPSLLPGRMG LENESLLAGY THERIIQPPL GRVCGSSQAA GSRRAPLASG PEGVEELVGK PAFVMEPRQE MEKESTCVLM KPNTEIKLPV EVDIGLTQAE GPDETKNTEP QMGLVIEPPQ CQFAQQHEQR KEAGNIESGV EPPDRIRPIY SGKFFDRTPC WPSAGKVIPV GYRVATCLTE KLPRLITPPE AKKYFNFRYP PAGVERVFYG RANDPQIAPY LTHGIRSKIS VLANTLINPQ PITTFQQKIK DKKESIYLSN RRAPLGKSHD QAPGLPKGMD TTNTTFGTAV IKEYSAKDVV NPPKSYEEVF KEGNEGHDLY VVSHNDYYAG EAKNRKYNPS SFHRCSVYGV PTPHFNDGRA MAKSLYWLHE LQMKRGAKFV SKRADDFKEK FQHKLGRVLD PIAETMNVPP DCTFGACLRP EEYGVGDLIH NRLPDEYLRG KDRQRALIAA VRHHLKKVNY QKFDTLLAAF RHYDKKGDGM IDKDELQEAC DQANLSLDDK LLDQLFDYCD VDNDGFINYL EFANFLNWKD KMLLKEYEER VIIKGRKPDC VNPTEANVEE PEQTLLIKPE DIVLKEAGST EKTLRTLLRP SDKVSNYYKT TSSEINAIVG AIPSTCYPIC GVPTIRSDIP APRIRRISDR TNYGEEGSAY SLLYPTIFAR KGVFERDFFK TRSKEEIAEI LCNIGVKLSD EEFENVWNLA SKKHHRGEVC VENIRNVLDE LRHADRIKCK TLM //