EFHD1_HUMAN
ID EFHD1_HUMAN Reviewed; 239 AA.
AC Q9BUP0; B2RD83; E9PFH3; Q9BTF8; Q9H8I2; Q9HBQ0;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=EF-hand domain-containing protein D1;
DE AltName: Full=EF-hand domain-containing protein 1;
DE AltName: Full=Swiprosin-2;
GN Name=EFHD1; Synonyms=SWS2; ORFNames=PP3051;
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).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ARG-186.
RC TISSUE=Heart, Placenta, and Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-186.
RC TISSUE=Eye, and 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF ASP-103; GLU-114; ASP-139 AND GLU-150.
RX PubMed=26975899; DOI=10.1016/j.ceca.2016.03.002;
RA Hou T., Jian C., Xu J., Huang A.Y., Xi J., Hu K., Wei L., Cheng H.,
RA Wang X.;
RT "Identification of EFHD1 as a novel Ca(2+) sensor for mitoflash
RT activation.";
RL Cell Calcium 59:262-270(2016).
CC -!- FUNCTION: Acts as a calcium sensor for mitochondrial flash (mitoflash)
CC activation, an event characterized by stochastic bursts of superoxide
CC production (PubMed:26975899). May play a role in neuronal
CC differentiation (By similarity). {ECO:0000250|UniProtKB:Q9D4J1,
CC ECO:0000269|PubMed:26975899}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9D4J1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BUP0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BUP0-2; Sequence=VSP_045541;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG17248.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF218006; AAG17248.1; ALT_FRAME; mRNA.
DR EMBL; AK023674; BAB14634.1; -; mRNA.
DR EMBL; AK310565; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK315442; BAG37830.1; -; mRNA.
DR EMBL; AC064852; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073254; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002449; AAH02449.1; -; mRNA.
DR EMBL; BC004128; AAH04128.2; -; mRNA.
DR CCDS; CCDS2497.1; -. [Q9BUP0-1]
DR CCDS; CCDS58755.1; -. [Q9BUP0-2]
DR RefSeq; NP_001230181.1; NM_001243252.1. [Q9BUP0-2]
DR RefSeq; NP_001295324.1; NM_001308395.1.
DR RefSeq; NP_079478.1; NM_025202.3. [Q9BUP0-1]
DR AlphaFoldDB; Q9BUP0; -.
DR SMR; Q9BUP0; -.
DR BioGRID; 123216; 80.
DR IntAct; Q9BUP0; 17.
DR STRING; 9606.ENSP00000264059; -.
DR iPTMnet; Q9BUP0; -.
DR PhosphoSitePlus; Q9BUP0; -.
DR BioMuta; EFHD1; -.
DR DMDM; 20140222; -.
DR EPD; Q9BUP0; -.
DR jPOST; Q9BUP0; -.
DR MassIVE; Q9BUP0; -.
DR MaxQB; Q9BUP0; -.
DR PaxDb; Q9BUP0; -.
DR PeptideAtlas; Q9BUP0; -.
DR PRIDE; Q9BUP0; -.
DR ProteomicsDB; 20103; -.
DR ProteomicsDB; 79116; -. [Q9BUP0-1]
DR Antibodypedia; 34436; 305 antibodies from 30 providers.
DR DNASU; 80303; -.
DR Ensembl; ENST00000264059.8; ENSP00000264059.3; ENSG00000115468.13. [Q9BUP0-1]
DR Ensembl; ENST00000409613.5; ENSP00000386556.1; ENSG00000115468.13. [Q9BUP0-2]
DR GeneID; 80303; -.
DR KEGG; hsa:80303; -.
DR MANE-Select; ENST00000264059.8; ENSP00000264059.3; NM_025202.4; NP_079478.1.
DR UCSC; uc002vtc.4; human. [Q9BUP0-1]
DR CTD; 80303; -.
DR DisGeNET; 80303; -.
DR GeneCards; EFHD1; -.
DR HGNC; HGNC:29556; EFHD1.
DR HPA; ENSG00000115468; Tissue enhanced (brain).
DR MIM; 611617; gene.
DR neXtProt; NX_Q9BUP0; -.
DR OpenTargets; ENSG00000115468; -.
DR PharmGKB; PA134935372; -.
DR VEuPathDB; HostDB:ENSG00000115468; -.
DR eggNOG; KOG0041; Eukaryota.
DR GeneTree; ENSGT00390000012058; -.
DR HOGENOM; CLU_094429_0_0_1; -.
DR InParanoid; Q9BUP0; -.
DR OMA; RQDINEG; -.
DR OrthoDB; 1511376at2759; -.
DR PhylomeDB; Q9BUP0; -.
DR TreeFam; TF320736; -.
DR PathwayCommons; Q9BUP0; -.
DR SignaLink; Q9BUP0; -.
DR BioGRID-ORCS; 80303; 10 hits in 1077 CRISPR screens.
DR ChiTaRS; EFHD1; human.
DR GenomeRNAi; 80303; -.
DR Pharos; Q9BUP0; Tbio.
DR PRO; PR:Q9BUP0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9BUP0; protein.
DR Bgee; ENSG00000115468; Expressed in inferior olivary complex and 189 other tissues.
DR ExpressionAtlas; Q9BUP0; baseline and differential.
DR Genevisible; Q9BUP0; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0061891; F:calcium ion sensor activity; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:1900069; P:regulation of cellular hyperosmotic salinity response; IMP:UniProtKB.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR040365; EFHD1/2.
DR PANTHER; PTHR13025; PTHR13025; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..239
FT /note="EF-hand domain-containing protein D1"
FT /id="PRO_0000073643"
FT DOMAIN 90..125
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 126..161
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..45
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 103
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 107
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 139
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 141
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 143
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 145
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 150
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..101
FT /note="MASEELACKLERRLRREEAEESGPQLAPLGAPAPEPKPEPEPPARAPTASAD
FT AELSAQLSRRLDINEGAARPRRCRVFNPYTEFPEFSRRLIKDLESMFKL -> MGELQ
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045541"
FT VARIANT 186
FT /note="K -> R (in dbSNP:rs11550699)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_047966"
FT MUTAGEN 103
FT /note="D->A: In mtEFHD1; abolished ability to enhance
FT mitoflash activity; when associated with K-114; A-139 and
FT K-150."
FT /evidence="ECO:0000269|PubMed:26975899"
FT MUTAGEN 114
FT /note="E->K: In mtEFHD1; abolished ability to enhance
FT mitoflash activity; when associated with A-103; A-139 and
FT K-150."
FT /evidence="ECO:0000269|PubMed:26975899"
FT MUTAGEN 139
FT /note="D->A: In mtEFHD1; abolished ability to enhance
FT mitoflash activity; when associated with A-103; K-114 and
FT K-150."
FT /evidence="ECO:0000269|PubMed:26975899"
FT MUTAGEN 150
FT /note="E->K: In mtEFHD1; abolished ability to enhance
FT mitoflash activity; when associated with A-103; K-114 and
FT A-139."
FT /evidence="ECO:0000269|PubMed:26975899"
SQ SEQUENCE 239 AA; 26928 MW; 1712F79E2A3CC007 CRC64;
MASEELACKL ERRLRREEAE ESGPQLAPLG APAPEPKPEP EPPARAPTAS ADAELSAQLS
RRLDINEGAA RPRRCRVFNP YTEFPEFSRR LIKDLESMFK LYDAGRDGFI DLMELKLMME
KLGAPQTHLG LKSMIKEVDE DFDGKLSFRE FLLIFHKAAA GELQEDSGLM ALAKLSEIDV
ALEGVKGAKN FFEAKVQALS SASKFEAELK AEQDERKREE EERRLRQAAF QKLKANFNT
