AHSP_HUMAN
ID AHSP_HUMAN Reviewed; 102 AA.
AC Q9NZD4; Q8TD01;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Alpha-hemoglobin-stabilizing protein;
DE AltName: Full=Erythroid differentiation-related factor;
DE AltName: Full=Erythroid-associated factor;
GN Name=AHSP; Synonyms=EDRF, ERAF;
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], AND TISSUE SPECIFICITY.
RX PubMed=11231637; DOI=10.1038/85515;
RA Miele G., Manson J., Clinton M.;
RT "A novel erythroid-specific marker of transmissible spongiform
RT encephalopathies.";
RL Nat. Med. 7:361-364(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Michel U., Schulz-Schaeffer W.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Finning K., Anstee D.;
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12066189; DOI=10.1038/nature00803;
RA Kihm A.J., Kong Y., Hong W., Russell J.E., Rouda S., Adachi K., Simon M.C.,
RA Blobel G.A., Weiss M.J.;
RT "An abundant erythroid protein that stabilizes free alpha-haemoglobin.";
RL Nature 417:758-763(2002).
RN [7]
RP CHARACTERIZATION.
RX PubMed=12192002; DOI=10.1074/jbc.m206084200;
RA Gell D., Kong Y., Eaton S.A., Weiss M.J., Mackay J.P.;
RT "Biophysical characterization of the alpha-globin binding protein alpha-
RT hemoglobin stabilizing protein.";
RL J. Biol. Chem. 277:40602-40609(2002).
RN [8]
RP STRUCTURE BY NMR OF 1-90, AND X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN
RP COMPLEX WITH HBA.
RX PubMed=15550245; DOI=10.1016/j.cell.2004.11.025;
RA Feng L., Gell D.A., Zhou S., Gu L., Kong Y., Li J., Hu M., Yan N., Lee C.,
RA Rich A.M., Armstrong R.S., Lay P.A., Gow A.J., Weiss M.J., Mackay J.P.,
RA Shi Y.;
RT "Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin.";
RL Cell 119:629-640(2004).
RN [9]
RP STRUCTURE BY NMR OF 2-102 OF WILD TYPE AND MUTANT ALA-30.
RX PubMed=15178680; DOI=10.1074/jbc.m405016200;
RA Santiveri C.M., Perez-Canadillas J.M., Vadivelu M.K., Allen M.D.,
RA Rutherford T.J., Watkins N.A., Bycroft M.;
RT "NMR structure of the alpha-hemoglobin stabilizing protein: insights into
RT conformational heterogeneity and binding.";
RL J. Biol. Chem. 279:34963-34970(2004).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH HBA.
RX PubMed=15931225; DOI=10.1038/nature03609;
RA Feng L., Zhou S., Gu L., Gell D.A., Mackay J.P., Weiss M.J., Gow A.J.,
RA Shi Y.;
RT "Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective
RT mechanism for haem.";
RL Nature 435:697-701(2005).
CC -!- FUNCTION: Acts as a chaperone to prevent the harmful aggregation of
CC alpha-hemoglobin during normal erythroid cell development. Specifically
CC protects free alpha-hemoglobin from precipitation. It is predicted to
CC modulate pathological states of alpha-hemoglobin excess such as beta-
CC thalassemia. {ECO:0000269|PubMed:12066189}.
CC -!- SUBUNIT: Monomer. Forms a heterodimer with free alpha-hemoglobin. Does
CC not bind beta-hemoglobin nor alpha(2)beta(2) hemoglobin A.
CC {ECO:0000269|PubMed:15550245, ECO:0000269|PubMed:15931225}.
CC -!- INTERACTION:
CC Q9NZD4; Q8IUQ0: CLVS1; NbExp=3; IntAct=EBI-720250, EBI-9657824;
CC Q9NZD4; P62942: FKBP1A; NbExp=3; IntAct=EBI-720250, EBI-1027571;
CC Q9NZD4; P69905: HBA2; NbExp=2; IntAct=EBI-720250, EBI-714680;
CC Q9NZD4; P20618: PSMB1; NbExp=3; IntAct=EBI-720250, EBI-372273;
CC Q9NZD4; Q05086-2: UBE3A; NbExp=3; IntAct=EBI-720250, EBI-10175863;
CC Q9NZD4; Q9Y2B5: VPS9D1; NbExp=3; IntAct=EBI-720250, EBI-9031083;
CC Q9NZD4; Q5D1E8: ZC3H12A; NbExp=4; IntAct=EBI-720250, EBI-747793;
CC Q9NZD4; P17024: ZNF20; NbExp=3; IntAct=EBI-720250, EBI-717634;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12066189}.
CC -!- TISSUE SPECIFICITY: Expressed in blood and bone marrow.
CC {ECO:0000269|PubMed:11231637, ECO:0000269|PubMed:12066189}.
CC -!- INDUCTION: By GATA1 during erythroid maturation.
CC -!- SIMILARITY: Belongs to the AHSP family. {ECO:0000305}.
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; AF364517; AAK50856.1; -; mRNA.
DR EMBL; AF208865; AAF64279.1; -; mRNA.
DR EMBL; AY072612; AAL82894.1; -; Genomic_DNA.
DR EMBL; AF485325; AAO49381.1; -; Genomic_DNA.
DR EMBL; BC035842; AAH35842.1; -; mRNA.
DR CCDS; CCDS10716.1; -.
DR RefSeq; NP_001305150.1; NM_001318221.1.
DR RefSeq; NP_001305151.1; NM_001318222.1.
DR RefSeq; NP_057717.1; NM_016633.3.
DR PDB; 1W09; NMR; -; A=3-94.
DR PDB; 1W0A; NMR; -; A=3-94.
DR PDB; 1W0B; NMR; -; A=2-102.
DR PDB; 1XZY; NMR; -; A=1-90.
DR PDB; 1Y01; X-ray; 2.80 A; A=1-102.
DR PDB; 1Z8U; X-ray; 2.40 A; A/C=1-102.
DR PDB; 3IA3; X-ray; 3.20 A; A/C=1-91.
DR PDB; 3OVU; X-ray; 2.83 A; A=2-102.
DR PDBsum; 1W09; -.
DR PDBsum; 1W0A; -.
DR PDBsum; 1W0B; -.
DR PDBsum; 1XZY; -.
DR PDBsum; 1Y01; -.
DR PDBsum; 1Z8U; -.
DR PDBsum; 3IA3; -.
DR PDBsum; 3OVU; -.
DR AlphaFoldDB; Q9NZD4; -.
DR BMRB; Q9NZD4; -.
DR SMR; Q9NZD4; -.
DR BioGRID; 119476; 16.
DR DIP; DIP-35198N; -.
DR IntAct; Q9NZD4; 10.
DR STRING; 9606.ENSP00000307199; -.
DR DrugBank; DB14490; Ferrous ascorbate.
DR DrugBank; DB14491; Ferrous fumarate.
DR DrugBank; DB14488; Ferrous gluconate.
DR DrugBank; DB14501; Ferrous glycine sulfate.
DR DrugBank; DB14489; Ferrous succinate.
DR DrugBank; DB01592; Iron.
DR BioMuta; AHSP; -.
DR DMDM; 23813669; -.
DR MassIVE; Q9NZD4; -.
DR PaxDb; Q9NZD4; -.
DR PeptideAtlas; Q9NZD4; -.
DR PRIDE; Q9NZD4; -.
DR ProteomicsDB; 83376; -.
DR TopDownProteomics; Q9NZD4; -.
DR Antibodypedia; 27920; 187 antibodies from 23 providers.
DR DNASU; 51327; -.
DR Ensembl; ENST00000302312.9; ENSP00000307199.4; ENSG00000169877.10.
DR GeneID; 51327; -.
DR KEGG; hsa:51327; -.
DR MANE-Select; ENST00000302312.9; ENSP00000307199.4; NM_016633.4; NP_057717.1.
DR UCSC; uc002ecj.4; human.
DR CTD; 51327; -.
DR DisGeNET; 51327; -.
DR GeneCards; AHSP; -.
DR HGNC; HGNC:18075; AHSP.
DR HPA; ENSG00000169877; Tissue enriched (bone).
DR MIM; 605821; gene.
DR neXtProt; NX_Q9NZD4; -.
DR OpenTargets; ENSG00000169877; -.
DR PharmGKB; PA27842; -.
DR VEuPathDB; HostDB:ENSG00000169877; -.
DR eggNOG; ENOG502SXDF; Eukaryota.
DR GeneTree; ENSGT00390000003648; -.
DR HOGENOM; CLU_188032_0_0_1; -.
DR InParanoid; Q9NZD4; -.
DR OMA; DWIKFYL; -.
DR OrthoDB; 1573941at2759; -.
DR PhylomeDB; Q9NZD4; -.
DR TreeFam; TF337056; -.
DR PathwayCommons; Q9NZD4; -.
DR SignaLink; Q9NZD4; -.
DR SIGNOR; Q9NZD4; -.
DR BioGRID-ORCS; 51327; 9 hits in 1070 CRISPR screens.
DR ChiTaRS; AHSP; human.
DR EvolutionaryTrace; Q9NZD4; -.
DR GeneWiki; ERAF; -.
DR GenomeRNAi; 51327; -.
DR Pharos; Q9NZD4; Tbio.
DR PRO; PR:Q9NZD4; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9NZD4; protein.
DR Bgee; ENSG00000169877; Expressed in trabecular bone tissue and 113 other tissues.
DR ExpressionAtlas; Q9NZD4; baseline and differential.
DR Genevisible; Q9NZD4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005833; C:hemoglobin complex; NAS:UniProtKB.
DR GO; GO:0030492; F:hemoglobin binding; NAS:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; NAS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IBA:GO_Central.
DR GO; GO:0020027; P:hemoglobin metabolic process; NAS:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0050821; P:protein stabilization; IBA:GO_Central.
DR InterPro; IPR015317; A_Hb_stabilising_prot.
DR InterPro; IPR036468; AHSP_sf.
DR PANTHER; PTHR15914; PTHR15914; 1.
DR Pfam; PF09236; AHSP; 1.
DR SUPFAM; SSF109751; SSF109751; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Cytoplasm; Reference proteome.
FT CHAIN 1..102
FT /note="Alpha-hemoglobin-stabilizing protein"
FT /id="PRO_0000064509"
FT VARIANT 100
FT /note="P -> T (in dbSNP:rs36018996)"
FT /id="VAR_050650"
FT CONFLICT 32
FT /note="V -> A (in Ref. 3; AAL82894)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="D -> N (in Ref. 3; AAL82894)"
FT /evidence="ECO:0000305"
FT HELIX 5..23
FT /evidence="ECO:0007829|PDB:1Z8U"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:1Z8U"
FT HELIX 34..52
FT /evidence="ECO:0007829|PDB:1Z8U"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:1Z8U"
FT HELIX 60..86
FT /evidence="ECO:0007829|PDB:1Z8U"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1W0B"
SQ SEQUENCE 102 AA; 11840 MW; 275DDF8BC670EF20 CRC64;
MALLKANKDL ISAGLKEFSV LLNQQVFNDP LVSEEDMVTV VEDWMNFYIN YYRQQVTGEP
QERDKALQEL RQELNTLANP FLAKYRDFLK SHELPSHPPP SS
