HBAZ_HUMAN
ID HBAZ_HUMAN Reviewed; 142 AA.
AC P02008; Q6IBF6;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Hemoglobin subunit zeta;
DE AltName: Full=HBAZ;
DE AltName: Full=Hemoglobin zeta chain;
DE AltName: Full=Zeta-globin;
GN Name=HBZ; Synonyms=HBZ2;
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 [GENOMIC DNA].
RX PubMed=6297773; DOI=10.1016/0092-8674(82)90311-7;
RA Proudfoot N.J., Gil A., Maniatis T.;
RT "The structure of the human zeta-globin gene and a closely linked, nearly
RT identical pseudogene.";
RL Cell 31:553-563(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6963223; DOI=10.1089/dna.1982.1.355;
RA Cohen-Solal M., Authier B., Deriel J.K., Murnane M.J., Forget B.G.;
RT "Cloning and nucleotide sequence analysis of human embryonic zeta-globin
RT cDNA.";
RL DNA 1:355-363(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9054936; DOI=10.1038/ng0397-252;
RA Flint J., Thomas K., Micklem G., Raynham H., Clark K., Doggett N.A.,
RA King A., Higgs D.R.;
RT "The relationship between chromosome structure and function at a human
RT telomeric region.";
RL Nat. Genet. 15:252-257(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [6]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas, and Spleen;
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 [8]
RP PROTEIN SEQUENCE OF 2-142, AND DEVELOPMENTAL STAGE.
RX PubMed=6179844;
RA Aschauer H., Sanguansermsri T., Braunitzer G.;
RT "Human embryonic haemoglobins. The primary structure of the zeta chains.";
RL Hoppe-Seyler's Z. Physiol. Chem. 362:1159-1162(1981).
RN [9]
RP PROTEIN SEQUENCE OF 2-142, DEVELOPMENTAL STAGE, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=6171809; DOI=10.1073/pnas.78.10.6076;
RA Clegg J.B., Gagnon J.;
RT "Structure of the zeta chain of human embryonic hemoglobin.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:6076-6080(1981).
RN [10]
RP ACETYLATION AT SER-2.
RX PubMed=6172357;
RA Aschauer H., Schaefer W., Sanguansermsri T., Braunitzer G.;
RT "Human embryonic haemoglobins. Ac-Ser-Leu-Thr-is the N-terminal sequence of
RT the zeta-chains.";
RL Hoppe-Seyler's Z. Physiol. Chem. 362:1657-1659(1981).
RN [11]
RP SUBUNIT, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=6539334; DOI=10.1016/s0021-9258(17)39875-7;
RA Randhawa Z.I., Jones R.T., Lie-Injo L.E.;
RT "Human hemoglobin Portland II (zeta 2 beta 2). Isolation and
RT characterization of Portland hemoglobin components and their constituent
RT globin chains.";
RL J. Biol. Chem. 259:7325-7330(1984).
RN [12]
RP DEVELOPMENTAL STAGE.
RX PubMed=1939469; DOI=10.1016/0378-4347(91)80142-y;
RA Kutlar F., Moscoso H., Kiefer C.R., Garver F.A., Beksac S., Onderoglu L.,
RA Gurgey A., Altay C., Huisman T.H.;
RT "Quantities of adult, fetal and embryonic globin chains in the blood of
RT eighteen- to twenty-week-old human fetuses.";
RL J. Chromatogr. B 567:359-368(1991).
RN [13]
RP SUBUNIT, AND DEVELOPMENTAL STAGE.
RX PubMed=20925047; DOI=10.1002/pd.2619;
RA Li T.K., Leung K.Y., Lam Y.H., Tang M.H., Chan V.;
RT "Haemoglobin level, proportion of haemoglobin Bart's and haemoglobin
RT Portland in fetuses affected by homozygous alpha0-thalassemia from 12 to 40
RT weeks' gestation.";
RL Prenat. Diagn. 30:1126-1130(2010).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-29; SER-53; SER-73 AND
RP SER-82, AND 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH HEME AND MOUSE HBB,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND SUBUNIT.
RX PubMed=11747442; DOI=10.1021/bi011329f;
RA Kidd R.D., Russell J.E., Watmough N.J., Baker E.N., Brittain T.;
RT "The role of beta chains in the control of the hemoglobin oxygen binding
RT function: chimeric human/mouse proteins, structure, and function.";
RL Biochemistry 40:15669-15675(2001).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH HEME; CARBON
RP MONOXIDE AND HBB, AND SUBUNIT.
RX PubMed=24100324; DOI=10.1107/s0907444913019197;
RA Safo M.K., Ko T.P., Abdulmalik O., He Z., Wang A.H., Schreiter E.R.,
RA Russell J.E.;
RT "Structure of fully liganded Hb zeta2beta2s trapped in a tense
RT conformation.";
RL Acta Crystallogr. D 69:2061-2071(2013).
CC -!- FUNCTION: The zeta chain is an alpha-type chain of mammalian embryonic
CC hemoglobin.
CC -!- SUBUNIT: Heterotetramer of two zeta chains and two epsilon chains in
CC early embryonic hemoglobin Gower-1; two zeta chains and two gamma
CC chains in fetal hemoglobin Portland-1. Heterotetramer of two zeta
CC chains and two beta chains in hemoglobin Portland-2, detected in
CC fetuses and neonates with homozygous alpha-thalassemia.
CC {ECO:0000269|PubMed:11747442, ECO:0000269|PubMed:20925047,
CC ECO:0000269|PubMed:24100324, ECO:0000269|PubMed:6171809,
CC ECO:0000269|PubMed:6539334}.
CC -!- INTERACTION:
CC P02008; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-719843, EBI-3866279;
CC P02008; O95273: CCNDBP1; NbExp=3; IntAct=EBI-719843, EBI-748961;
CC P02008; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-719843, EBI-3867333;
CC P02008; Q8NF50-2: DOCK8; NbExp=3; IntAct=EBI-719843, EBI-10174653;
CC P02008; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-719843, EBI-5916454;
CC P02008; P68871: HBB; NbExp=7; IntAct=EBI-719843, EBI-715554;
CC P02008; P02042: HBD; NbExp=8; IntAct=EBI-719843, EBI-6152722;
CC P02008; P02100: HBE1; NbExp=6; IntAct=EBI-719843, EBI-6190240;
CC P02008; Q6B0K9: HBM; NbExp=3; IntAct=EBI-719843, EBI-12805802;
CC P02008; P09105: HBQ1; NbExp=3; IntAct=EBI-719843, EBI-10193656;
CC P02008; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-719843, EBI-7060731;
CC P02008; Q5VWX1: KHDRBS2; NbExp=4; IntAct=EBI-719843, EBI-742808;
CC P02008; O75525: KHDRBS3; NbExp=3; IntAct=EBI-719843, EBI-722504;
CC P02008; Q15323: KRT31; NbExp=3; IntAct=EBI-719843, EBI-948001;
CC P02008; Q6A162: KRT40; NbExp=3; IntAct=EBI-719843, EBI-10171697;
CC P02008; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-719843, EBI-10172290;
CC P02008; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-719843, EBI-10172052;
CC P02008; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-719843, EBI-11522433;
CC P02008; Q7Z3S9: NOTCH2NLA; NbExp=4; IntAct=EBI-719843, EBI-945833;
CC P02008; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-719843, EBI-22310682;
CC P02008; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-719843, EBI-741158;
CC P02008; P0DJD3-2: RBMY1A1; NbExp=3; IntAct=EBI-719843, EBI-11994018;
CC -!- TISSUE SPECIFICITY: Detected in fetal erythrocytes (at protein level).
CC {ECO:0000269|PubMed:6171809, ECO:0000269|PubMed:6539334}.
CC -!- DEVELOPMENTAL STAGE: Detected in the yolk sac of the early embryo and
CC in erythrocytes from fetal umbilical cord blood. Detected at low levels
CC after 10 weeks of gestation. Hemoglobin Portland levels are increased
CC in fetuses with homozygous alpha-thalassemia, but it constitutes only a
CC minor proportion of total hemoglobin and its levels decrease steadily
CC after 10 weeks of gestation. Hemoglobin Portland-2 is detected in blood
CC from still-born neoneates with homozygous alpha-thalassemia (at protein
CC level). {ECO:0000269|PubMed:1939469, ECO:0000269|PubMed:20925047,
CC ECO:0000269|PubMed:6171809, ECO:0000269|PubMed:6179844,
CC ECO:0000269|PubMed:6539334}.
CC -!- SIMILARITY: Belongs to the globin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00238}.
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DR EMBL; J00182; AAB59406.1; -; Genomic_DNA.
DR EMBL; M24173; AAA61306.1; -; mRNA.
DR EMBL; Z84721; CAB06552.1; -; Genomic_DNA.
DR EMBL; CR456848; CAG33129.1; -; mRNA.
DR EMBL; AE006462; AAK61214.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85864.1; -; Genomic_DNA.
DR EMBL; BC027892; AAH27892.1; -; mRNA.
DR CCDS; CCDS10397.1; -.
DR PIR; A90832; HZHU.
DR RefSeq; NP_005323.1; NM_005332.2.
DR RefSeq; XP_005255345.1; XM_005255288.3.
DR PDB; 1JEB; X-ray; 2.10 A; A/C=2-142.
DR PDB; 3W4U; X-ray; 1.95 A; A/C/E=1-142.
DR PDBsum; 1JEB; -.
DR PDBsum; 3W4U; -.
DR AlphaFoldDB; P02008; -.
DR SMR; P02008; -.
DR BioGRID; 109300; 47.
DR ComplexPortal; CPX-2928; Embryonic hemoglobin Gower-1 complex.
DR ComplexPortal; CPX-2929; Hemoglobin Portland-2 complex.
DR ComplexPortal; CPX-2930; Hemoglobin Portland-1 Variant 1 complex.
DR ComplexPortal; CPX-2931; Hemoglobin Portland-1 Variant 2 complex.
DR IntAct; P02008; 32.
DR STRING; 9606.ENSP00000252951; -.
DR iPTMnet; P02008; -.
DR PhosphoSitePlus; P02008; -.
DR BioMuta; HBZ; -.
DR DMDM; 122335; -.
DR jPOST; P02008; -.
DR MassIVE; P02008; -.
DR MaxQB; P02008; -.
DR PaxDb; P02008; -.
DR PeptideAtlas; P02008; -.
DR PRIDE; P02008; -.
DR ProteomicsDB; 51514; -.
DR Antibodypedia; 8877; 277 antibodies from 30 providers.
DR DNASU; 3050; -.
DR Ensembl; ENST00000252951.3; ENSP00000252951.2; ENSG00000130656.6.
DR GeneID; 3050; -.
DR KEGG; hsa:3050; -.
DR MANE-Select; ENST00000252951.3; ENSP00000252951.2; NM_005332.3; NP_005323.1.
DR UCSC; uc002cft.2; human.
DR CTD; 3050; -.
DR DisGeNET; 3050; -.
DR GeneCards; HBZ; -.
DR GeneReviews; HBZ; -.
DR HGNC; HGNC:4835; HBZ.
DR HPA; ENSG00000130656; Group enriched (bone marrow, testis).
DR MalaCards; HBZ; -.
DR MIM; 142310; gene.
DR neXtProt; NX_P02008; -.
DR OpenTargets; ENSG00000130656; -.
DR PharmGKB; PA29212; -.
DR VEuPathDB; HostDB:ENSG00000130656; -.
DR eggNOG; KOG3378; Eukaryota.
DR GeneTree; ENSGT00940000158623; -.
DR HOGENOM; CLU_003827_10_2_1; -.
DR InParanoid; P02008; -.
DR OMA; VTIWAKV; -.
DR OrthoDB; 1398217at2759; -.
DR PhylomeDB; P02008; -.
DR TreeFam; TF332328; -.
DR PathwayCommons; P02008; -.
DR SignaLink; P02008; -.
DR BioGRID-ORCS; 3050; 9 hits in 1035 CRISPR screens.
DR ChiTaRS; HBZ; human.
DR EvolutionaryTrace; P02008; -.
DR GeneWiki; HBZ; -.
DR GenomeRNAi; 3050; -.
DR Pharos; P02008; Tbio.
DR PRO; PR:P02008; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P02008; protein.
DR Bgee; ENSG00000130656; Expressed in left testis and 81 other tissues.
DR ExpressionAtlas; P02008; baseline and differential.
DR Genevisible; P02008; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031838; C:haptoglobin-hemoglobin complex; IBA:GO_Central.
DR GO; GO:0005833; C:hemoglobin complex; IPI:ComplexPortal.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0043177; F:organic acid binding; IBA:GO_Central.
DR GO; GO:0019825; F:oxygen binding; IBA:GO_Central.
DR GO; GO:0005344; F:oxygen carrier activity; IBA:GO_Central.
DR GO; GO:0015670; P:carbon dioxide transport; IC:ComplexPortal.
DR GO; GO:0098869; P:cellular oxidant detoxification; IEA:GOC.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IBA:GO_Central.
DR GO; GO:0015671; P:oxygen transport; IDA:ComplexPortal.
DR GO; GO:0010942; P:positive regulation of cell death; IC:ComplexPortal.
DR CDD; cd08927; Hb-alpha-like; 1.
DR Gene3D; 1.10.490.10; -; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like_sf.
DR InterPro; IPR012292; Globin/Proto.
DR InterPro; IPR002338; Hemoglobin_a-typ.
DR InterPro; IPR002340; Hemoglobin_zeta.
DR Pfam; PF00042; Globin; 1.
DR PRINTS; PR00612; ALPHAHAEM.
DR PRINTS; PR00816; ZETAHAEM.
DR SUPFAM; SSF46458; SSF46458; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Heme; Iron;
KW Metal-binding; Oxygen transport; Phosphoprotein; Reference proteome;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11747442,
FT ECO:0000269|PubMed:6171809, ECO:0000269|PubMed:6172357,
FT ECO:0000269|PubMed:6179844"
FT CHAIN 2..142
FT /note="Hemoglobin subunit zeta"
FT /id="PRO_0000052851"
FT BINDING 59
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="distal binding residue"
FT BINDING 88
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:11747442,
FT ECO:0000269|PubMed:6172357"
FT MOD_RES 29
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT HELIX 5..19
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 22..36
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 38..43
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 54..72
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:3W4U"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 97..113
FT /evidence="ECO:0007829|PDB:3W4U"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 120..137
FT /evidence="ECO:0007829|PDB:3W4U"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:1JEB"
SQ SEQUENCE 142 AA; 15637 MW; B62A9B825743A155 CRC64;
MSLTKTERTI IVSMWAKIST QADTIGTETL ERLFLSHPQT KTYFPHFDLH PGSAQLRAHG
SKVVAAVGDA VKSIDDIGGA LSKLSELHAY ILRVDPVNFK LLSHCLLVTL AARFPADFTA
EAHAAWDKFL SVVSSVLTEK YR
