EFHB_HUMAN
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 03-AUG-2022, entry version 136.
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).
CC -!- FUNCTION: Cytosolic sensor for calcium, modulates the interaction of
CC STIM1 and ORAI1 upon store depletion and the activation of store-
CC operated Ca(2+) entry (SOCE) and NFAT translocation from cytosol to
CC nucleus (PubMed:30481768). Microtubule inner protein (MIP) part of the
CC dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is
CC required for motile cilia beating (By similarity).
CC {ECO:0000250|UniProtKB:F1MMV1, ECO:0000269|PubMed:30481768}.
CC -!- SUBUNIT: Interacts with STIM1 and ORAI1; the interactions take place
CC upon Ca(2+)-store depletion and dissociate through a Ca(2+)-dependent
CC mechanism. Interaction with STIM1 inhibits STIM1 interaction with
CC SARAF. {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 {ECO:0000305|PubMed:30481768}.
CC Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000250|UniProtKB:F1MMV1}.
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 -!- 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};
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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 AlphaFoldDB; Q8N7U6; -.
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; Q8N7U6; -.
DR PeptideAtlas; Q8N7U6; -.
DR PRIDE; Q8N7U6; -.
DR ProteomicsDB; 72328; -. [Q8N7U6-1]
DR ProteomicsDB; 72329; -. [Q8N7U6-2]
DR ProteomicsDB; 72330; -. [Q8N7U6-3]
DR Antibodypedia; 27043; 109 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 CTD; 151651; -.
DR DisGeNET; 151651; -.
DR GeneCards; EFHB; -.
DR HGNC; HGNC:26330; EFHB.
DR HPA; ENSG00000163576; Group enriched (brain, 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; WAPLGKS; -.
DR OrthoDB; 1016066at2759; -.
DR PhylomeDB; Q8N7U6; -.
DR TreeFam; TF323832; -.
DR PathwayCommons; Q8N7U6; -.
DR SignaLink; Q8N7U6; -.
DR BioGRID-ORCS; 151651; 13 hits in 1070 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 104 other tissues.
DR ExpressionAtlas; Q8N7U6; baseline and differential.
DR Genevisible; Q8N7U6; HS.
DR GO; GO:0005879; C:axonemal microtubule; ISS:UniProtKB.
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: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 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; PTHR12086; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium transport; Cell projection;
KW Cytoplasm; Cytoskeleton; Ion transport; Metal-binding; Reference proteome;
KW Repeat; 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
