FUND1_HUMAN
ID FUND1_HUMAN Reviewed; 155 AA.
AC Q8IVP5;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=FUN14 domain-containing protein 1;
GN Name=FUNDC1;
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 GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY,
RP PHOSPHORYLATION AT TYR-18, INTERACTION WITH MAP1LC3A; MAP1LC3B AND GABARAP,
RP AND MUTAGENESIS OF TYR-18; LEU-21 AND 31-TRP-TRP-32.
RX PubMed=22267086; DOI=10.1038/ncb2422;
RA Liu L., Feng D., Chen G., Chen M., Zheng Q., Song P., Ma Q., Zhu C.,
RA Wang R., Qi W., Huang L., Xue P., Li B., Wang X., Jin H., Wang J., Yang F.,
RA Liu P., Zhu Y., Sui S., Chen Q.;
RT "Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced
RT mitophagy in mammalian cells.";
RL Nat. Cell Biol. 14:177-185(2012).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP VARIANT VAL-56.
RX PubMed=24700572; DOI=10.1002/ajmg.a.36508;
RA Barboza-Cerda M.C., Wong L.J., Martinez-de-Villarreal L.E., Zhang V.W.,
RA Dector M.A.;
RT "A novel EBP c.224T>A mutation supports the existence of a male-specific
RT disorder independent of CDPX2.";
RL Am. J. Med. Genet. A 164A:1642-1647(2014).
CC -!- FUNCTION: Acts as an activator of hypoxia-induced mitophagy, an
CC important mechanism for mitochondrial quality control.
CC {ECO:0000269|PubMed:22267086}.
CC -!- SUBUNIT: Interacts (via YXXL motif) with MAP1 LC3 family proteins
CC MAP1LC3A, MAP1LC3B and GABARAP. {ECO:0000269|PubMed:22267086}.
CC -!- INTERACTION:
CC Q8IVP5; P56545: CTBP2; NbExp=3; IntAct=EBI-3059266, EBI-741533;
CC Q8IVP5; Q08426: EHHADH; NbExp=4; IntAct=EBI-3059266, EBI-2339219;
CC Q8IVP5; P60520: GABARAPL2; NbExp=4; IntAct=EBI-3059266, EBI-720116;
CC Q8IVP5; Q9H492: MAP1LC3A; NbExp=4; IntAct=EBI-3059266, EBI-720768;
CC Q8IVP5; Q9GZQ8: MAP1LC3B; NbExp=8; IntAct=EBI-3059266, EBI-373144;
CC Q8IVP5; Q96E29: MTERF3; NbExp=3; IntAct=EBI-3059266, EBI-7825321;
CC Q8IVP5; Q9HC62: SENP2; NbExp=3; IntAct=EBI-3059266, EBI-714881;
CC Q8IVP5; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-3059266, EBI-2623095;
CC Q8IVP5; Q96AG3: SLC25A46; NbExp=3; IntAct=EBI-3059266, EBI-10281975;
CC Q8IVP5; Q13596: SNX1; NbExp=3; IntAct=EBI-3059266, EBI-2822329;
CC Q8IVP5; A0A384ME17: TUFM; NbExp=3; IntAct=EBI-3059266, EBI-12261790;
CC Q8IVP5; P49411: TUFM; NbExp=3; IntAct=EBI-3059266, EBI-359097;
CC Q8IVP5; P07947: YES1; NbExp=4; IntAct=EBI-3059266, EBI-515331;
CC Q8IVP5; O70405: Ulk1; Xeno; NbExp=3; IntAct=EBI-3059266, EBI-8390771;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:22267086}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:22267086}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:22267086}.
CC -!- DOMAIN: The YXXL motif mediates the interaction with MAP1 LC3 family
CC proteins MAP1LC3A, MAP1LC3B and GABARAP. {ECO:0000269|PubMed:22267086}.
CC -!- PTM: Phosphorylation at Tyr-18 by SRC inhibits activation of mitophagy.
CC Following hypoxia, dephosphorylated at Tyr-18, leading to interaction
CC with MAP1 LC3 family proteins and triggering mitophagy.
CC {ECO:0000269|PubMed:22267086}.
CC -!- SIMILARITY: Belongs to the FUN14 family. {ECO:0000305}.
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DR EMBL; AL136137; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL022163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035015; AAH35015.1; -; mRNA.
DR EMBL; BC042813; AAH42813.1; -; mRNA.
DR CCDS; CCDS14263.1; -.
DR RefSeq; NP_776155.1; NM_173794.3.
DR PDB; 2N9X; NMR; -; B=10-26.
DR PDB; 5GMV; X-ray; 2.25 A; C/D=16-23.
DR PDBsum; 2N9X; -.
DR PDBsum; 5GMV; -.
DR AlphaFoldDB; Q8IVP5; -.
DR BMRB; Q8IVP5; -.
DR SMR; Q8IVP5; -.
DR BioGRID; 126561; 30.
DR IntAct; Q8IVP5; 18.
DR MINT; Q8IVP5; -.
DR STRING; 9606.ENSP00000367284; -.
DR iPTMnet; Q8IVP5; -.
DR PhosphoSitePlus; Q8IVP5; -.
DR SwissPalm; Q8IVP5; -.
DR BioMuta; FUNDC1; -.
DR DMDM; 74750673; -.
DR EPD; Q8IVP5; -.
DR jPOST; Q8IVP5; -.
DR MassIVE; Q8IVP5; -.
DR MaxQB; Q8IVP5; -.
DR PaxDb; Q8IVP5; -.
DR PeptideAtlas; Q8IVP5; -.
DR PRIDE; Q8IVP5; -.
DR ProteomicsDB; 70750; -.
DR Antibodypedia; 25165; 242 antibodies from 27 providers.
DR DNASU; 139341; -.
DR Ensembl; ENST00000378045.5; ENSP00000367284.4; ENSG00000069509.6.
DR GeneID; 139341; -.
DR KEGG; hsa:139341; -.
DR MANE-Select; ENST00000378045.5; ENSP00000367284.4; NM_173794.4; NP_776155.1.
DR UCSC; uc004dgc.4; human.
DR CTD; 139341; -.
DR DisGeNET; 139341; -.
DR GeneCards; FUNDC1; -.
DR HGNC; HGNC:28746; FUNDC1.
DR HPA; ENSG00000069509; Low tissue specificity.
DR MIM; 300871; gene.
DR neXtProt; NX_Q8IVP5; -.
DR OpenTargets; ENSG00000069509; -.
DR PharmGKB; PA134875965; -.
DR VEuPathDB; HostDB:ENSG00000069509; -.
DR eggNOG; KOG4099; Eukaryota.
DR GeneTree; ENSGT00940000154517; -.
DR HOGENOM; CLU_095425_2_0_1; -.
DR InParanoid; Q8IVP5; -.
DR OMA; ATVDHRE; -.
DR OrthoDB; 1431148at2759; -.
DR PhylomeDB; Q8IVP5; -.
DR TreeFam; TF300280; -.
DR PathwayCommons; Q8IVP5; -.
DR Reactome; R-HSA-8934903; Receptor Mediated Mitophagy.
DR SignaLink; Q8IVP5; -.
DR BioGRID-ORCS; 139341; 12 hits in 705 CRISPR screens.
DR ChiTaRS; FUNDC1; human.
DR GeneWiki; FUNDC1; -.
DR GenomeRNAi; 139341; -.
DR Pharos; Q8IVP5; Tbio.
DR PRO; PR:Q8IVP5; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8IVP5; protein.
DR Bgee; ENSG00000069509; Expressed in left ventricle myocardium and 184 other tissues.
DR Genevisible; Q8IVP5; HS.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:MGI.
DR GO; GO:0000422; P:autophagy of mitochondrion; IDA:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR InterPro; IPR007014; FUN14.
DR PANTHER; PTHR21346; PTHR21346; 1.
DR Pfam; PF04930; FUN14; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..155
FT /note="FUN14 domain-containing protein 1"
FT /id="PRO_0000271345"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..74
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT MOTIF 18..21
FT /note="YXXL"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 18
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:22267086"
FT VARIANT 56
FT /note="M -> V (in dbSNP:rs189499062)"
FT /evidence="ECO:0000269|PubMed:24700572"
FT /id="VAR_074638"
FT MUTAGEN 18
FT /note="Y->A: Impairs interaction with MAP1 LC3 family
FT proteins."
FT /evidence="ECO:0000269|PubMed:22267086"
FT MUTAGEN 18
FT /note="Y->W: Abolishes phosphorylation by SRC."
FT /evidence="ECO:0000269|PubMed:22267086"
FT MUTAGEN 21
FT /note="L->A: Impairs interaction with MAP1 LC3 family
FT proteins."
FT /evidence="ECO:0000269|PubMed:22267086"
FT MUTAGEN 32..33
FT /note="WW->AA: Does not affect interaction with MAP1 LC3
FT family proteins."
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:2N9X"
SQ SEQUENCE 155 AA; 17178 MW; 4E9ABF640795F0A9 CRC64;
MATRNPPPQD YESDDDSYEV LDLTEYARRH QWWNRVFGHS SGPMVEKYSV ATQIVMGGVT
GWCAGFLFQK VGKLAATAVG GGFLLLQIAS HSGYVQIDWK RVEKDVNKAK RQIKKRANKA
APEINNLIEE ATEFIKQNIV ISSGFVGGFL LGLAS
