ID KLF1_HUMAN Reviewed; 362 AA. AC Q13351; Q6PIJ5; Q92899; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JAN-2024, entry version 189. DE RecName: Full=Krueppel-like factor 1; DE AltName: Full=Erythroid krueppel-like transcription factor; DE Short=EKLF; GN Name=KLF1; Synonyms=EKLF; 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], AND TISSUE SPECIFICITY. RX PubMed=8924208; DOI=10.1089/dna.1996.15.347; RA Bieker J.J.; RT "Isolation, genomic structure, and expression of human erythroid Kruppel- RT like factor (EKLF)."; RL DNA Cell Biol. 15:347-352(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=9119377; DOI=10.1006/geno.1996.4472; RA van Ree J.H., Roskrow M.A., Becher A.M., McNall R., Valentine V.A., RA Jane S.M., Cunningham J.M.; RT "The human erythroid-specific transcription factor EKLF localizes to RT chromosome 19p13.12-p13.13."; RL Genomics 39:393-395(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-102. RC TISSUE=Lung; 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 [5] RP ACETYLATION, AND INTERACTION WITH CBP; EP300 AND PCAF. RX PubMed=9707565; DOI=10.1073/pnas.95.17.9855; RA Zhang W., Bieker J.J.; RT "Acetylation and modulation of erythroid Krueppel-like factor (EKLF) RT activity by interaction with histone acetyltransferases."; RL Proc. Natl. Acad. Sci. U.S.A. 95:9855-9860(1998). RN [6] RP ROLE IN ERYTHROPOIESIS, FUNCTION AS TRANSCRIPTIONAL ACTIVATOR OF CD44 AND RP AQP1, SUBCELLULAR LOCATION, VARIANT PRO-102, VARIANT CDAN4 LYS-325, AND RP CHARACTERIZATION OF VARIANT CDAN4 LYS-325. RX PubMed=21055716; DOI=10.1016/j.ajhg.2010.10.010; RA Arnaud L., Saison C., Helias V., Lucien N., Steschenko D., Giarratana M.C., RA Prehu C., Foliguet B., Montout L., de Brevern A.G., Francina A., RA Ripoche P., Fenneteau O., Da Costa L., Peyrard T., Coghlan G., Illum N., RA Birgens H., Tamary H., Iolascon A., Delaunay J., Tchernia G., Cartron J.P.; RT "A dominant mutation in the gene encoding the erythroid transcription RT factor KLF1 causes a congenital dyserythropoietic anemia."; RL Am. J. Hum. Genet. 87:721-727(2010). RN [7] RP FUNCTION AS REGULATOR OF FETAL-TO-ADULT GLOBIN SWITCHING, AND POLYMORPHISM. RX PubMed=20676099; DOI=10.1038/ng.630; RA Borg J., Papadopoulos P., Georgitsi M., Gutierrez L., Grech G., Fanis P., RA Phylactides M., Verkerk A.J., van der Spek P.J., Scerri C.A., Cassar W., RA Galdies R., van Ijcken W., Ozgur Z., Gillemans N., Hou J., Bugeja M., RA Grosveld F.G., von Lindern M., Felice A.E., Patrinos G.P., Philipsen S.; RT "Haploinsufficiency for the erythroid transcription factor KLF1 causes RT hereditary persistence of fetal hemoglobin."; RL Nat. Genet. 42:801-805(2010). RN [8] RP 9AATAD MOTIF. RX PubMed=31375868; DOI=10.1007/s00018-019-03251-w; RA Piskacek M., Havelka M., Jendruchova K., Knight A., Keegan L.P.; RT "The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with RT valines and intron reservoirs."; RL Cell. Mol. Life Sci. 77:1793-1810(2020). RN [9] RP STRUCTURE BY NMR OF 51-90 IN COMPLEX WITH YEAST TFB1, FUNCTION, AND RP INTERACTION WITH TFB1; CREBBP AND EP300. RX PubMed=21670263; DOI=10.1073/pnas.1017029108; RA Mas C., Lussier-Price M., Soni S., Morse T., Arseneault G., Di Lello P., RA Lafrance-Vanasse J., Bieker J.J., Omichinski J.G.; RT "Structural and functional characterization of an atypical activation RT domain in erythroid Kruppel-like factor (EKLF)."; RL Proc. Natl. Acad. Sci. U.S.A. 108:10484-10489(2011). RN [10] RP VARIANTS BLOOD GROUP-IN(LU) TYR-299; LEU-328; HIS-328 AND GLY-331, AND RP POLYMORPHISM. RX PubMed=18487511; DOI=10.1182/blood-2008-03-145672; RA Singleton B.K., Burton N.M., Green C., Brady R.L., Anstee D.J.; RT "Mutations in EKLF/KLF1 form the molecular basis of the rare blood group RT In(Lu) phenotype."; RL Blood 112:2081-2088(2008). RN [11] RP VARIANTS LYS-5; PRO-298; ASP-299; ARG-334 AND TYR-341. RX PubMed=24829204; DOI=10.1182/blood-2014-03-561779; RA Liu D., Zhang X., Yu L., Cai R., Ma X., Zheng C., Zhou Y., Liu Q., Wei X., RA Lin L., Yan T., Huang J., Mohandas N., An X., Xu X.; RT "KLF1 mutations are relatively more common in a thalassemia endemic region RT and ameliorate the severity of beta-thalassemia."; RL Blood 124:803-811(2014). RN [12] RP VARIANTS PRO-298 AND SER-338, CHARACTERIZATION OF VARIANTS PRO-298 AND RP SER-338, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=25585695; DOI=10.1038/ejhg.2014.291; RA Huang J., Zhang X., Liu D., Wei X., Shang X., Xiong F., Yu L., Yin X., RA Xu X.; RT "Compound heterozygosity for KLF1 mutations is associated with microcytic RT hypochromic anemia and increased fetal hemoglobin."; RL Eur. J. Hum. Genet. 23:1341-1348(2015). RN [13] RP VARIANT TRP-316. RX PubMed=25690802; DOI=10.3109/03630269.2015.1008702; RA Nitta T., Kawano F., Yamashiro Y., Takagi F., Murata T., Tanaka T., RA Ferania M., Adhiyanto C., Hattori Y.; RT "A new Krueppel-like factor 1 mutation (c.947G > A or p.C316Y) in humans RT causes beta-thalassemia minor."; RL Hemoglobin 39:121-126(2015). CC -!- FUNCTION: Transcription regulator of erythrocyte development that CC probably serves as a general switch factor during erythropoiesis. Is a CC dual regulator of fetal-to-adult globin switching. Binds to the CACCC CC box in the beta-globin gene promoter and acts as a preferential CC activator of this gene. Furthermore, it binds to the BCL11A promoter CC and activates expression of BCL11A, which in turn represses the HBG1 CC and HBG2 genes. This dual activity ensures that, in most adults, fetal CC hemoglobin levels are low. Able to activate CD44 and AQP1 promoters. CC When sumoylated, acts as a transcriptional repressor by promoting CC interaction with CDH2/MI2beta and also represses megakaryocytic CC differentiation. {ECO:0000250|UniProtKB:P46099, CC ECO:0000269|PubMed:25585695}. CC -!- SUBUNIT: Interacts with PCAF; the interaction does not acetylate EKLF CC and inhibits its transactivation activity (By similarity). Interacts CC with CREBBP/CBP and EP300; the interactions enhance the transactivation CC activity. Interacts with TFB1. {ECO:0000250, CC ECO:0000269|PubMed:21670263, ECO:0000269|PubMed:9707565}. CC -!- INTERACTION: CC Q13351; Q07021: C1QBP; NbExp=3; IntAct=EBI-8284732, EBI-347528; CC Q13351; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-8284732, EBI-10961624; CC Q13351; Q92793: CREBBP; NbExp=2; IntAct=EBI-8284732, EBI-81215; CC Q13351; Q92997: DVL3; NbExp=3; IntAct=EBI-8284732, EBI-739789; CC Q13351; O95967: EFEMP2; NbExp=3; IntAct=EBI-8284732, EBI-743414; CC Q13351; P32780: GTF2H1; NbExp=2; IntAct=EBI-8284732, EBI-715539; CC Q13351; P13807: GYS1; NbExp=3; IntAct=EBI-8284732, EBI-740553; CC Q13351; P52597: HNRNPF; NbExp=3; IntAct=EBI-8284732, EBI-352986; CC Q13351; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-8284732, EBI-7060731; CC Q13351; Q13064: MKRN3; NbExp=3; IntAct=EBI-8284732, EBI-2340269; CC Q13351; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-8284732, EBI-11022007; CC Q13351; Q15365: PCBP1; NbExp=3; IntAct=EBI-8284732, EBI-946095; CC Q13351; P79522: PRR3; NbExp=3; IntAct=EBI-8284732, EBI-2803328; CC Q13351; P98175: RBM10; NbExp=3; IntAct=EBI-8284732, EBI-721525; CC Q13351; Q9BQ04: RBM4B; NbExp=3; IntAct=EBI-8284732, EBI-715531; CC Q13351; Q6ZRY4: RBPMS2; NbExp=3; IntAct=EBI-8284732, EBI-11987469; CC Q13351; P09234: SNRPC; NbExp=3; IntAct=EBI-8284732, EBI-766589; CC Q13351; Q01085-2: TIAL1; NbExp=3; IntAct=EBI-8284732, EBI-11064654; CC Q13351; Q08117-2: TLE5; NbExp=3; IntAct=EBI-8284732, EBI-11741437; CC Q13351; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-8284732, EBI-2559305; CC Q13351; P32776: TFB1; Xeno; NbExp=3; IntAct=EBI-8284732, EBI-19146; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21055716, CC ECO:0000269|PubMed:25585695}. Note=Colocalizes with SUMO1 in nuclear CC speckles. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expression restricted to adult bone marrow and CC fetal liver. Not expressed in myeloid nor lymphoid cell lines. CC {ECO:0000269|PubMed:8924208, ECO:0000269|PubMed:9119377}. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:31375868}. CC -!- PTM: Acetylated; can be acetylated on both Lys-274 and Lys-288. CC Acetylation on Lys-274 (by CBP) appears to be the major site affecting CC EKLF transactivation activity (By similarity). {ECO:0000250}. CC -!- PTM: Sumoylated; sumoylation, promoted by PIAS1, leads to repression of CC megakaryocyte differentiation. Also promotes the interaction with the CC CDH4 subunit of the NuRD repression complex (By similarity). CC {ECO:0000250}. CC -!- PTM: Phosphorylated primarily on serine residues in the transactivation CC domain. Phosphorylation on Thr-23 is critical for the transactivation CC activity (By similarity). {ECO:0000250}. CC -!- POLYMORPHISM: Genetic variations in KLF1 underlie the fetal hemoglobin CC quantitative trait locus 6 (HBFQTL6) [MIM:613566]. Classic hereditary CC persistence of fetal hemoglobin (HPFH) is characterized by a CC substantial elevation of fetal hemoglobin (HbF) in adult red blood CC cells. There are no other phenotypic or hematologic manifestations. In CC healthy adults, fetal hemoglobin (HbF) is present at residual levels CC (less than 0.06% of total hemoglobin) with over 20-fold variation. Ten CC to fifteen percent of adults fall within the upper tail of the CC distribution. {ECO:0000269|PubMed:20676099}. CC -!- POLYMORPHISM: Genetic variations in KLF1 underlie the blood group- CC Lutheran inhibitor (In(Lu)) phenotype [MIM:111150]; also known as CC dominant Lu (a-b-) phenotype. In(Lu) is characterized phenotypically by CC the apparent absence of the Lu antigen (BCAM) on red blood cells during CC serologic tests: Lu(a-b-). {ECO:0000269|PubMed:18487511}. CC -!- DISEASE: Anemia, congenital dyserythropoietic, 4 (CDAN4) [MIM:613673]: CC A blood disorder characterized by ineffective erythropoiesis and CC hemolysis resulting in anemia. Circulating erythroblasts and CC erythroblasts in the bone marrow show various morphologic CC abnormalities. Affected individuals with CDA4 also have increased CC levels of fetal hemoglobin. {ECO:0000269|PubMed:21055716, CC ECO:0000269|PubMed:25585695}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC 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; U37106; AAC50562.1; -; Genomic_DNA. DR EMBL; U65404; AAC51108.1; -; mRNA. DR EMBL; AD000092; AAB51173.1; -; Genomic_DNA. DR EMBL; BC033580; AAH33580.1; -; mRNA. DR CCDS; CCDS12285.1; -. DR PIR; T45072; T45072. DR RefSeq; NP_006554.1; NM_006563.4. DR PDB; 2L2I; NMR; -; B=51-90. DR PDB; 2MBH; NMR; -; B=2-40. DR PDB; 2N23; NMR; -; B=22-40. DR PDBsum; 2L2I; -. DR PDBsum; 2MBH; -. DR PDBsum; 2N23; -. DR AlphaFoldDB; Q13351; -. DR BMRB; Q13351; -. DR SMR; Q13351; -. DR BioGRID; 115904; 36. DR DIP; DIP-43776N; -. DR IntAct; Q13351; 23. DR MINT; Q13351; -. DR STRING; 9606.ENSP00000264834; -. DR ChEMBL; CHEMBL3407313; -. DR iPTMnet; Q13351; -. DR PhosphoSitePlus; Q13351; -. DR BioMuta; KLF1; -. DR DMDM; 2501699; -. DR jPOST; Q13351; -. DR MassIVE; Q13351; -. DR MaxQB; Q13351; -. DR PaxDb; 9606-ENSP00000264834; -. DR PeptideAtlas; Q13351; -. DR ProteomicsDB; 59335; -. DR Pumba; Q13351; -. DR Antibodypedia; 13415; 439 antibodies from 38 providers. DR DNASU; 10661; -. DR Ensembl; ENST00000264834.6; ENSP00000264834.3; ENSG00000105610.6. DR GeneID; 10661; -. DR KEGG; hsa:10661; -. DR MANE-Select; ENST00000264834.6; ENSP00000264834.3; NM_006563.5; NP_006554.1. DR UCSC; uc002mvo.4; human. DR AGR; HGNC:6345; -. DR CTD; 10661; -. DR DisGeNET; 10661; -. DR GeneCards; KLF1; -. DR HGNC; HGNC:6345; KLF1. DR HPA; ENSG00000105610; Tissue enriched (bone). DR MalaCards; KLF1; -. DR MIM; 111150; phenotype. DR MIM; 600599; gene. DR MIM; 613566; phenotype. DR MIM; 613673; phenotype. DR neXtProt; NX_Q13351; -. DR OpenTargets; ENSG00000105610; -. DR Orphanet; 293825; Congenital dyserythropoietic anemia type IV. DR Orphanet; 46532; Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome. DR Orphanet; 251380; Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome. DR PharmGKB; PA30131; -. DR VEuPathDB; HostDB:ENSG00000105610; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000161856; -. DR HOGENOM; CLU_063878_0_0_1; -. DR InParanoid; Q13351; -. DR OMA; PFPDTQE; -. DR OrthoDB; 5484790at2759; -. DR PhylomeDB; Q13351; -. DR TreeFam; TF350556; -. DR PathwayCommons; Q13351; -. DR SignaLink; Q13351; -. DR SIGNOR; Q13351; -. DR BioGRID-ORCS; 10661; 47 hits in 1183 CRISPR screens. DR EvolutionaryTrace; Q13351; -. DR GenomeRNAi; 10661; -. DR Pharos; Q13351; Tbio. DR PRO; PR:Q13351; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q13351; Protein. DR Bgee; ENSG00000105610; Expressed in trabecular bone tissue and 63 other cell types or tissues. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd21581; KLF1_N; 1. DR DisProt; DP01640; -. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 3. DR IDEAL; IID00468; -. DR InterPro; IPR031786; EKLF_TAD1. DR InterPro; IPR031784; EKLF_TAD2. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR23235:SF133; KRUEPPEL-LIKE FACTOR 1; 1. DR PANTHER; PTHR23235; KRUEPPEL-LIKE TRANSCRIPTION FACTOR; 1. DR Pfam; PF16832; EKLF_TAD1; 1. DR Pfam; PF16833; EKLF_TAD2; 1. DR Pfam; PF00096; zf-C2H2; 3. DR SMART; SM00355; ZnF_C2H2; 3. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. DR Genevisible; Q13351; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Congenital dyserythropoietic anemia; KW Disease variant; DNA-binding; Hereditary hemolytic anemia; Isopeptide bond; KW Metal-binding; Methylation; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1..362 FT /note="Krueppel-like factor 1" FT /id="PRO_0000047160" FT ZN_FING 279..303 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 309..333 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 339..361 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 1..110 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 249..271 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 71..79 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:31375868" FT COMPBIAS 1..19 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 23 FT /note="Phosphothreonine; by CK2" FT /evidence="ECO:0000250|UniProtKB:P46099, ECO:0000305" FT MOD_RES 184 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P46099" FT MOD_RES 274 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P46099" FT MOD_RES 288 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P46099" FT CROSSLNK 54 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT VARIANT 5 FT /note="E -> K (in dbSNP:rs483352842)" FT /evidence="ECO:0000269|PubMed:24829204" FT /id="VAR_074272" FT VARIANT 102 FT /note="S -> P (in dbSNP:rs2072597)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:21055716" FT /id="VAR_043981" FT VARIANT 182 FT /note="F -> L (in dbSNP:rs2072596)" FT /id="VAR_043982" FT VARIANT 298 FT /note="A -> P (found in a patient with autosomal recessive FT microcytic hypochromic anemia and increased fetal FT hemoglobin; uncertain significance; no effect on protein FT abundance; no effect on protein localization; decreased FT transcriptional activity; dbSNP:rs387907598)" FT /evidence="ECO:0000269|PubMed:24829204, FT ECO:0000269|PubMed:25585695" FT /id="VAR_072737" FT VARIANT 299 FT /note="H -> D (in dbSNP:rs137852688)" FT /evidence="ECO:0000269|PubMed:24829204" FT /id="VAR_074273" FT VARIANT 299 FT /note="H -> Y (in blood group-In(Lu); dbSNP:rs137852688)" FT /evidence="ECO:0000269|PubMed:18487511" FT /id="VAR_058108" FT VARIANT 316 FT /note="C -> W" FT /evidence="ECO:0000269|PubMed:25690802" FT /id="VAR_074274" FT VARIANT 325 FT /note="E -> K (in CDAN4; has a dominant-negative effect on FT the transcriptional activation of CD44 and AQP1 promoters; FT dbSNP:rs267607201)" FT /evidence="ECO:0000269|PubMed:21055716" FT /id="VAR_064901" FT VARIANT 328 FT /note="R -> H (in blood group-In(Lu); dbSNP:rs140252918)" FT /evidence="ECO:0000269|PubMed:18487511" FT /id="VAR_058109" FT VARIANT 328 FT /note="R -> L (in blood group-In(Lu))" FT /evidence="ECO:0000269|PubMed:18487511" FT /id="VAR_058110" FT VARIANT 331 FT /note="R -> G (in blood group-In(Lu))" FT /evidence="ECO:0000269|PubMed:18487511" FT /id="VAR_058111" FT VARIANT 334 FT /note="T -> R (in dbSNP:rs483352841)" FT /evidence="ECO:0000269|PubMed:24829204" FT /id="VAR_074275" FT VARIANT 338 FT /note="P -> S (found in a patient with autosomal recessive FT microcytic hypochromic anemia and increased fetal FT hemoglobin; with microcytic hypochromic anemia; no effect FT on protein abundance; no effect on protein localization; FT decreased transcriptional activity; dbSNP:rs387907599)" FT /evidence="ECO:0000269|PubMed:25585695" FT /id="VAR_072738" FT VARIANT 341 FT /note="C -> Y (in dbSNP:rs483352839)" FT /evidence="ECO:0000269|PubMed:24829204" FT /id="VAR_074276" FT CONFLICT 163 FT /note="A -> G (in Ref. 2; AAC51108)" FT /evidence="ECO:0000305" FT CONFLICT 173 FT /note="P -> A (in Ref. 2; AAC51108)" FT /evidence="ECO:0000305" FT CONFLICT 184 FT /note="R -> G (in Ref. 2; AAC51108)" FT /evidence="ECO:0000305" FT CONFLICT 192 FT /note="A -> E (in Ref. 2; AAC51108)" FT /evidence="ECO:0000305" FT HELIX 24..35 FT /evidence="ECO:0007829|PDB:2MBH" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:2L2I" FT STRAND 70..75 FT /evidence="ECO:0007829|PDB:2L2I" SQ SEQUENCE 362 AA; 38221 MW; 6E9A48A2B6A37C76 CRC64; MATAETALPS ISTLTALGPF PDTQDDFLKW WRSEEAQDMG PGPPDPTEPP LHVKSEDQPG EEEDDERGAD ATWDLDLLLT NFSGPEPGGA PQTCALAPSE ASGAQYPPPP ETLGAYAGGP GLVAGLLGSE DHSGWVRPAL RARAPDAFVG PALAPAPAPE PKALALQPVY PGPGAGSSGG YFPRTGLSVP AASGAPYGLL SGYPAMYPAP QYQGHFQLFR GLQGPAPGPA TSPSFLSCLG PGTVGTGLGG TAEDPGVIAE TAPSKRGRRS WARKRQAAHT CAHPGCGKSY TKSSHLKAHL RTHTGEKPYA CTWEGCGWRF ARSDELTRHY RKHTGQRPFR CQLCPRAFSR SDHLALHMKR HL //