HEBP2_HUMAN
ID HEBP2_HUMAN Reviewed; 205 AA.
AC Q9Y5Z4; Q96P57;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Heme-binding protein 2;
DE AltName: Full=Placental protein 23;
DE Short=PP23;
DE AltName: Full=Protein SOUL;
GN Name=HEBP2; Synonyms=C6orf34, SOUL;
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] (ISOFORM 1).
RX PubMed=10640688; DOI=10.1016/s0169-328x(99)00277-6;
RA Zylka M.J., Reppert S.M.;
RT "Discovery of a putative heme-binding protein family (SOUL/HBP) by two-
RT tissue suppression subtractive hybridization and database searches.";
RL Brain Res. Mol. Brain Res. 74:175-181(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH LRPPRC.
RX PubMed=11827465; DOI=10.1006/geno.2001.6679;
RA Liu L., McKeehan W.L.;
RT "Sequence analysis of LRPPRC and its SEC1 domain interaction partners
RT suggests roles in cytoskeletal organization, vesicular trafficking,
RT nucleocytosolic shuttling, and chromosome activity.";
RL Genomics 79:124-136(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Szigeti A., Boronkai A., Bellyei S., Komlosi K., Melegh B., Sumegi B.,
RA Bohn H., Than G.N., Than N.G.;
RT "Isolation and sequence analysis of a cDNA encoding placental protein 23
RT (PP23).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye, and Placenta;
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 [6]
RP PROTEIN SEQUENCE OF 27-41; 48-76; 133-163; 173-184 AND 189-197, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=2018407; DOI=10.1007/bf02390087;
RA Bohn H., Winckler W.;
RT "Isolation and characterization of five new soluble placental tissue
RT proteins (PP22, PP23, PP24, PP25, PP26).";
RL Arch. Gynecol. Obstet. 248:111-115(1991).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17098234; DOI=10.1016/j.febslet.2006.10.067;
RA Szigeti A., Bellyei S., Gasz B., Boronkai A., Hocsak E., Minik O.,
RA Bognar Z., Varbiro G., Sumegi B., Gallyas F. Jr.;
RT "Induction of necrotic cell death and mitochondrial permeabilization by
RT heme binding protein 2/SOUL.";
RL FEBS Lett. 580:6447-6454(2006).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, 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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [14]
RP IDENTIFICATION BY 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 [15]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH BCL2L1, SUBUNIT,
RP DOMAIN, AND INTERACTION WITH BCL2L1.
RX PubMed=21639858; DOI=10.1042/bj20110257;
RA Ambrosi E., Capaldi S., Bovi M., Saccomani G., Perduca M., Monaco H.L.;
RT "Structural changes in the BH3 domain of SOUL protein upon interaction with
RT the anti-apoptotic protein Bcl-xL.";
RL Biochem. J. 438:291-301(2011).
RN [16] {ECO:0007744|PDB:5GQQ}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 20-197 IN COMPLEX WITH PDCD6, AND
RP INTERACTION WITH PDCD6.
RX PubMed=27784779; DOI=10.1074/jbc.m116.752444;
RA Ma J., Zhang X., Feng Y., Zhang H., Wang X., Zheng Y., Qiao W., Liu X.;
RT "Structural and functional study of apoptosis-linked gene-2.Heme-binding
RT protein 2 interactions in HIV-1 production.";
RL J. Biol. Chem. 291:26670-26685(2016).
CC -!- FUNCTION: Can promote mitochondrial permeability transition and
CC facilitate necrotic cell death under different types of stress
CC conditions. {ECO:0000269|PubMed:17098234}.
CC -!- SUBUNIT: Monomer. Interacts with LRPPRC (PubMed:11827465). May interact
CC with BCL2L1; an interaction with BCL2L1 was observed using a peptide,
CC but not with the full-length protein (PubMed:21639858). The full-length
CC protein would have to undergo a major conformation change for the
CC interaction to occur (PubMed:21639858). Interacts with PDCD6
CC (PubMed:27784779). {ECO:0000269|PubMed:11827465,
CC ECO:0000269|PubMed:17098234, ECO:0000269|PubMed:21639858,
CC ECO:0000269|PubMed:27784779}.
CC -!- INTERACTION:
CC Q9Y5Z4; O75340: PDCD6; NbExp=8; IntAct=EBI-741593, EBI-352915;
CC Q9Y5Z4; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-741593, EBI-742388;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17098234}.
CC Mitochondrion {ECO:0000269|PubMed:17098234}. Note=Mainly localized to
CC the cytoplasm with a much lower abundance in the mitochondrion.
CC {ECO:0000269|PubMed:17098234}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y5Z4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5Z4-2; Sequence=VSP_017057;
CC -!- TISSUE SPECIFICITY: Detected in placenta. {ECO:0000269|PubMed:2018407}.
CC -!- DOMAIN: Forms a distorted beta-barrel structure, with two helices that
CC are packed against the outer surface of the barrel.
CC {ECO:0000269|PubMed:21639858}.
CC -!- SIMILARITY: Belongs to the HEBP family. {ECO:0000305}.
CC -!- CAUTION: Has been described as heme-binding protein in mouse, but His-
CC 42, a residue essential for heme binding in mouse, is not conserved in
CC all orthologs, or in the heme-binding family member HEBP1.
CC {ECO:0000305}.
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DR EMBL; AF117616; AAD32099.1; -; mRNA.
DR EMBL; AF411610; AAL07394.1; -; mRNA.
DR EMBL; AY427823; AAR88624.1; -; mRNA.
DR EMBL; AL031003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008205; AAH08205.1; -; mRNA.
DR EMBL; BC010290; AAH10290.1; -; mRNA.
DR EMBL; BC093037; AAH93037.1; -; mRNA.
DR CCDS; CCDS5191.1; -. [Q9Y5Z4-1]
DR RefSeq; NP_055135.1; NM_014320.2. [Q9Y5Z4-1]
DR PDB; 3R85; X-ray; 1.95 A; E/F/G/H=147-172.
DR PDB; 3R8J; X-ray; 1.60 A; A/B=2-205.
DR PDB; 3R8K; X-ray; 2.85 A; A/B/C/D=2-205.
DR PDB; 4AYZ; X-ray; 3.50 A; A/B=1-205.
DR PDB; 4B0Y; X-ray; 3.50 A; A=1-205.
DR PDB; 5GQQ; X-ray; 2.20 A; A/B=20-197.
DR PDBsum; 3R85; -.
DR PDBsum; 3R8J; -.
DR PDBsum; 3R8K; -.
DR PDBsum; 4AYZ; -.
DR PDBsum; 4B0Y; -.
DR PDBsum; 5GQQ; -.
DR AlphaFoldDB; Q9Y5Z4; -.
DR SMR; Q9Y5Z4; -.
DR BioGRID; 117128; 9.
DR IntAct; Q9Y5Z4; 5.
DR STRING; 9606.ENSP00000475750; -.
DR iPTMnet; Q9Y5Z4; -.
DR MetOSite; Q9Y5Z4; -.
DR PhosphoSitePlus; Q9Y5Z4; -.
DR BioMuta; HEBP2; -.
DR DMDM; 74753513; -.
DR EPD; Q9Y5Z4; -.
DR jPOST; Q9Y5Z4; -.
DR MassIVE; Q9Y5Z4; -.
DR MaxQB; Q9Y5Z4; -.
DR PaxDb; Q9Y5Z4; -.
DR PeptideAtlas; Q9Y5Z4; -.
DR PRIDE; Q9Y5Z4; -.
DR ProteomicsDB; 86551; -. [Q9Y5Z4-1]
DR ProteomicsDB; 86552; -. [Q9Y5Z4-2]
DR Antibodypedia; 1915; 150 antibodies from 22 providers.
DR DNASU; 23593; -.
DR Ensembl; ENST00000607197.6; ENSP00000475750.1; ENSG00000051620.11. [Q9Y5Z4-1]
DR GeneID; 23593; -.
DR KEGG; hsa:23593; -.
DR MANE-Select; ENST00000607197.6; ENSP00000475750.1; NM_014320.3; NP_055135.1.
DR UCSC; uc003qhw.2; human. [Q9Y5Z4-1]
DR CTD; 23593; -.
DR DisGeNET; 23593; -.
DR GeneCards; HEBP2; -.
DR HGNC; HGNC:15716; HEBP2.
DR HPA; ENSG00000051620; Low tissue specificity.
DR MIM; 605825; gene.
DR neXtProt; NX_Q9Y5Z4; -.
DR OpenTargets; ENSG00000051620; -.
DR PharmGKB; PA25935; -.
DR VEuPathDB; HostDB:ENSG00000051620; -.
DR eggNOG; ENOG502RXJR; Eukaryota.
DR GeneTree; ENSGT00940000160412; -.
DR HOGENOM; CLU_068699_2_1_1; -.
DR InParanoid; Q9Y5Z4; -.
DR OMA; TAYVRTY; -.
DR OrthoDB; 1182055at2759; -.
DR PhylomeDB; Q9Y5Z4; -.
DR TreeFam; TF328887; -.
DR PathwayCommons; Q9Y5Z4; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9Y5Z4; -.
DR BioGRID-ORCS; 23593; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; HEBP2; human.
DR GeneWiki; HEBP2; -.
DR GenomeRNAi; 23593; -.
DR Pharos; Q9Y5Z4; Tbio.
DR PRO; PR:Q9Y5Z4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y5Z4; protein.
DR Bgee; ENSG00000051620; Expressed in parotid gland and 203 other tissues.
DR ExpressionAtlas; Q9Y5Z4; baseline and differential.
DR Genevisible; Q9Y5Z4; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0010917; P:negative regulation of mitochondrial membrane potential; IMP:UniProtKB.
DR GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; IMP:UniProtKB.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; IMP:UniProtKB.
DR Gene3D; 3.20.80.10; -; 1.
DR InterPro; IPR011256; Reg_factor_effector_dom_sf.
DR InterPro; IPR006917; SOUL_haem-bd.
DR PANTHER; PTHR11220; PTHR11220; 1.
DR Pfam; PF04832; SOUL; 1.
DR SUPFAM; SSF55136; SSF55136; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Mitochondrion; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..205
FT /note="Heme-binding protein 2"
FT /id="PRO_0000116900"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 12..33
FT /note="AEDAAAQAVETPGWKAPEDAGP -> F (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11827465"
FT /id="VSP_017057"
FT VARIANT 140
FT /note="R -> Q (in dbSNP:rs3734303)"
FT /id="VAR_053364"
FT VARIANT 191
FT /note="E -> A (in dbSNP:rs14812)"
FT /id="VAR_053365"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:3R8K"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:5GQQ"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 46..56
FT /evidence="ECO:0007829|PDB:3R8J"
FT HELIX 58..73
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:4AYZ"
FT STRAND 103..110
FT /evidence="ECO:0007829|PDB:3R8J"
FT HELIX 113..116
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 135..144
FT /evidence="ECO:0007829|PDB:3R8J"
FT HELIX 148..164
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 174..183
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:3R8J"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:3R8J"
SQ SEQUENCE 205 AA; 22875 MW; A0B5131F94783E07 CRC64;
MAEPLQPDPG AAEDAAAQAV ETPGWKAPED AGPQPGSYEI RHYGPAKWVS TSVESMDWDS
AIQTGFTKLN SYIQGKNEKE MKIKMTAPVT SYVEPGSGPF SESTITISLY IPSEQQFDPP
RPLESDVFIE DRAEMTVFVR SFDGFSSAQK NQEQLLTLAS ILREDGKVFD EKVYYTAGYN
SPVKLLNRNN EVWLIQKNEP TKENE
