HRK_HUMAN
ID HRK_HUMAN Reviewed; 91 AA.
AC O00198;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Activator of apoptosis harakiri;
DE AltName: Full=BH3-interacting domain-containing protein 3;
DE AltName: Full=Neuronal death protein DP5;
GN Name=HRK; Synonyms=BID3;
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 [MRNA], FUNCTION, AND INTERACTION WITH BCL2 AND BCL2L1.
RX PubMed=9130713; DOI=10.1093/emboj/16.7.1686;
RA Inohara N., Ding L., Chen S., Nunez G.;
RT "Harakiri, a novel regulator of cell death, encodes a protein that
RT activates apoptosis and interacts selectively with survival-promoting
RT proteins Bcl-2 and Bcl-X(L).";
RL EMBO J. 16:1686-1694(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP FUNCTION, INTERACTION WITH C1QBP AND BCL2L1, AND SUBCELLULAR LOCATION.
RX PubMed=15031724; DOI=10.1038/sj.cdd.4401418;
RA Sunayama J., Ando Y., Itoh N., Tomiyama A., Sakurada K., Sugiyama A.,
RA Kang D., Tashiro F., Gotoh Y., Kuchino Y., Kitanaka C.;
RT "Physical and functional interaction between BH3-only protein Hrk and
RT mitochondrial pore-forming protein p32.";
RL Cell Death Differ. 11:771-781(2004).
RN [4]
RP STRUCTURE BY NMR OF 22-91, SUBCELLULAR LOCATION, CIRCULAR DICHROISM, AND
RP INTERACTION WITH BCL2 AND BCL2L1.
RX PubMed=21731739; DOI=10.1371/journal.pone.0021413;
RA Barrera-Vilarmau S., Obregon P., de Alba E.;
RT "Intrinsic order and disorder in the BCL-2 member harakiri: insights into
RT its proapoptotic activity.";
RL PLoS ONE 6:E21413-E21413(2011).
CC -!- FUNCTION: Promotes apoptosis. {ECO:0000269|PubMed:15031724,
CC ECO:0000269|PubMed:9130713}.
CC -!- SUBUNIT: Interacts with BCL2 and BCL2L1. Interacts with C1QBP.
CC {ECO:0000269|PubMed:15031724, ECO:0000269|PubMed:21731739,
CC ECO:0000269|PubMed:9130713}.
CC -!- INTERACTION:
CC O00198; Q07817-1: BCL2L1; NbExp=3; IntAct=EBI-701322, EBI-287195;
CC O00198; Q07021: C1QBP; NbExp=7; IntAct=EBI-701322, EBI-347528;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein.
CC Mitochondrion.
CC -!- DOMAIN: The BH3 motif is required for the induction of cell death.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HRKID40865ch12q24.html";
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DR EMBL; U76376; AAC34931.1; -; mRNA.
DR EMBL; AC083806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS9181.1; -.
DR RefSeq; NP_003797.1; NM_003806.2.
DR RefSeq; XP_016875635.1; XM_017020146.1.
DR PDB; 2L58; NMR; -; A=22-53.
DR PDB; 2L5B; NMR; -; A=61-91.
DR PDB; 6XY4; X-ray; 2.05 A; B=26-51.
DR PDBsum; 2L58; -.
DR PDBsum; 2L5B; -.
DR PDBsum; 6XY4; -.
DR AlphaFoldDB; O00198; -.
DR SMR; O00198; -.
DR BioGRID; 114276; 6.
DR ELM; O00198; -.
DR IntAct; O00198; 7.
DR STRING; 9606.ENSP00000257572; -.
DR BioMuta; HRK; -.
DR MassIVE; O00198; -.
DR PaxDb; O00198; -.
DR PRIDE; O00198; -.
DR Antibodypedia; 18831; 208 antibodies from 29 providers.
DR DNASU; 8739; -.
DR Ensembl; ENST00000257572.5; ENSP00000257572.4; ENSG00000135116.9.
DR GeneID; 8739; -.
DR KEGG; hsa:8739; -.
DR MANE-Select; ENST00000257572.5; ENSP00000257572.4; NM_003806.4; NP_003797.1.
DR UCSC; uc001twe.5; human.
DR CTD; 8739; -.
DR DisGeNET; 8739; -.
DR GeneCards; HRK; -.
DR HGNC; HGNC:5185; HRK.
DR HPA; ENSG00000135116; Tissue enhanced (brain, thyroid gland).
DR MIM; 603447; gene.
DR neXtProt; NX_O00198; -.
DR OpenTargets; ENSG00000135116; -.
DR PharmGKB; PA29459; -.
DR VEuPathDB; HostDB:ENSG00000135116; -.
DR eggNOG; ENOG502T2F4; Eukaryota.
DR GeneTree; ENSGT00390000007050; -.
DR HOGENOM; CLU_2426351_0_0_1; -.
DR InParanoid; O00198; -.
DR OMA; QERTMWR; -.
DR OrthoDB; 1605284at2759; -.
DR PhylomeDB; O00198; -.
DR TreeFam; TF338168; -.
DR PathwayCommons; O00198; -.
DR SignaLink; O00198; -.
DR SIGNOR; O00198; -.
DR BioGRID-ORCS; 8739; 25 hits in 1060 CRISPR screens.
DR ChiTaRS; HRK; human.
DR EvolutionaryTrace; O00198; -.
DR GeneWiki; HRK_(gene); -.
DR GenomeRNAi; 8739; -.
DR Pharos; O00198; Tbio.
DR PRO; PR:O00198; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O00198; protein.
DR Bgee; ENSG00000135116; Expressed in buccal mucosa cell and 113 other tissues.
DR ExpressionAtlas; O00198; baseline and differential.
DR Genevisible; O00198; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:BHF-UCL.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IDA:BHF-UCL.
DR InterPro; IPR017249; Apoptosis_activator_harakiri.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR PANTHER; PTHR15056; PTHR15056; 1.
DR Pfam; PF15196; Harakiri; 1.
DR PIRSF; PIRSF037635; BID3; 1.
DR PROSITE; PS01259; BH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Membrane; Mitochondrion; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..91
FT /note="Activator of apoptosis harakiri"
FT /id="PRO_0000143106"
FT TRANSMEM 69..87
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 33..47
FT /note="BH3"
FT HELIX 29..49
FT /evidence="ECO:0007829|PDB:6XY4"
FT HELIX 69..85
FT /evidence="ECO:0007829|PDB:2L5B"
SQ SEQUENCE 91 AA; 9884 MW; 22E45FA2B0B7AA00 CRC64;
MCPCPLHRGR GPPAVCACSA GRLGLRSSAA QLTAARLKAL GDELHQRTMW RRRARSRRAP
APGALPTYWP WLCAAAQVAA LAAWLLGRRN L
