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 04-NOV-2026, entry version 226. 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 IN COMPLEX WITH HEME AND MOUSE HBB, CLEAVAGE OF RP 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 IN COMPLEX WITH HEME; CARBON MONOXIDE AND HBB, AND RP 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_005332.3. 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 AlphaFoldDB; P02008; -. DR MDposit; P02008; -. DR SMR; P02008; -. DR BioGRID; 109300; 51. 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 FunCoup; P02008; 85. DR IntAct; P02008; 44. DR STRING; 9606.ENSP00000252951; -. DR BindingDB; P02008; -. DR ChEMBL; CHEMBL6066981; -. DR iPTMnet; P02008; -. DR PhosphoSitePlus; P02008; -. DR BioMuta; HBZ; -. DR DMDM; 122335; -. DR jPOST; P02008; -. DR MassIVE; P02008; -. DR PaxDb; 9606-ENSP00000252951; -. DR PeptideAtlas; P02008; -. DR ProteomicsDB; 51514; -. DR Pumba; P02008; -. DR Antibodypedia; 8877; 310 antibodies from 32 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 AGR; HGNC:4835; -. DR ClinPGx; PA29212; -. 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 OpenTargets; ENSG00000130656; -. DR VEuPathDB; HostDB:ENSG00000130656; -. DR eggNOG; KOG3378; Eukaryota. DR GeneTree; ENSGT00940000158623; -. DR HOGENOM; CLU_003827_10_2_1; -. DR InParanoid; P02008; -. DR OMA; AHIVNLW; -. DR OrthoDB; 8751793at2759; -. DR PAN-GO; P02008; 6 GO annotations based on evolutionary models. DR PhylomeDB; P02008; -. DR PathwayCommons; P02008; -. DR SignaLink; P02008; -. DR Agora; ENSG00000130656; -. DR BioGRID-ORCS; 3050; 16 hits in 1107 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 male germ line stem cell (sensu Vertebrata) in testis and 82 other cell types or tissues. DR ExpressionAtlas; P02008; baseline and differential. 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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0020037; F:heme binding; IBA:GO_Central. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0019825; F:oxygen binding; IEA:InterPro. DR GO; GO:0005344; F:oxygen carrier activity; IBA:GO_Central. DR GO; GO:0015670; P:carbon dioxide transport; NAS:ComplexPortal. DR GO; GO:0048821; P:erythrocyte development; IBA:GO_Central. DR GO; GO:0015671; P:oxygen transport; IDA:ComplexPortal. DR CDD; cd08927; Hb-alpha-like; 1. DR FunFam; 1.10.490.10:FF:000002; Hemoglobin subunit alpha; 1. DR Gene3D; 1.10.490.10; Globins; 1. DR InterPro; IPR000971; Globin. DR InterPro; IPR009050; Globin-like_sf. DR InterPro; IPR012292; Globin/Proto. DR InterPro; IPR002338; Hemoglobin_a-typ. DR InterPro; IPR050056; Hemoglobin_oxygen_transport. DR InterPro; IPR002340; Hemoglobin_zeta. DR PANTHER; PTHR11442; HEMOGLOBIN FAMILY MEMBER; 1. DR PANTHER; PTHR11442:SF41; HEMOGLOBIN SUBUNIT ZETA; 1. DR Pfam; PF00042; Globin; 1. DR PRINTS; PR00612; ALPHAHAEM. DR PRINTS; PR00816; ZETAHAEM. DR SUPFAM; SSF46458; Globin-like; 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; Proteomics identification; KW Reference proteome; 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 DOMAIN 2..142 FT /note="Globin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00238" 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..86 FT /evidence="ECO:0007829|PDB:3W4U" FT HELIX 87..91 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 //