Full text data of AK1
AK1
[Confidence: high (present in two of the MS resources)]
Adenylate kinase isoenzyme 1; AK 1; 2.7.4.3; 2.7.4.6 (ATP-AMP transphosphorylase 1; ATP:AMP phosphotransferase; Adenylate monophosphate kinase; Myokinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Adenylate kinase isoenzyme 1; AK 1; 2.7.4.3; 2.7.4.6 (ATP-AMP transphosphorylase 1; ATP:AMP phosphotransferase; Adenylate monophosphate kinase; Myokinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00018342
IPI00018342 Adenylate kinase isoenzyme 1 This small ubiquitous enzyme is essential for maintenance, ATP + AMP = 2 ADP soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00018342 Adenylate kinase isoenzyme 1 This small ubiquitous enzyme is essential for maintenance, ATP + AMP = 2 ADP soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P00568
ID KAD1_HUMAN Reviewed; 194 AA.
AC P00568; Q9BVK9; Q9UQC7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-APR-2002, sequence version 3.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Adenylate kinase isoenzyme 1;
DE Short=AK 1;
DE EC=2.7.4.3;
DE EC=2.7.4.6;
DE AltName: Full=ATP-AMP transphosphorylase 1;
DE AltName: Full=ATP:AMP phosphotransferase;
DE AltName: Full=Adenylate monophosphate kinase;
DE AltName: Full=Myokinase;
GN Name=AK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Skeletal muscle;
RX PubMed=183954; DOI=10.1111/j.1432-1033.1976.tb10787.x;
RA von Zabern I., Wittmann-Liebold B., Untucht-Grau R., Schirmer R.H.,
RA Pai E.F.;
RT "Primary and tertiary structure of the principal human adenylate
RT kinase.";
RL Eur. J. Biochem. 68:281-290(1976).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HAAKD TRP-128.
RX PubMed=2542324;
RA Matsuura S., Igarashi M., Tanizawa Y., Yamada M., Kishi F., Kajii T.,
RA Fujii H., Miwa S., Sakurai M., Nakazawa A.;
RT "Human adenylate kinase deficiency associated with hemolytic anemia. A
RT single base substitution affecting solubility and catalytic activity
RT of the cytosolic adenylate kinase.";
RL J. Biol. Chem. 264:10148-10155(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RA Noma T.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 10-21; 32-44; 64-77; 89-97; 108-128; 156-166 AND
RP 172-194, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
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.,
RA Buerckstuemmer T., 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 [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23416111; DOI=10.1016/j.biocel.2013.02.004;
RA Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.;
RT "The human adenylate kinase 9 is a nucleoside mono- and diphosphate
RT kinase.";
RL Int. J. Biochem. Cell Biol. 45:925-931(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE
RP ANALOG AP5A.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human AK1A in complex with AP5A.";
RL Submitted (MAR-2007) to the PDB data bank.
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE
RP ANALOG AP4A.
RG Structural genomics consortium (SGC);
RT "Structure of adenylate kinase 1 in complex with P1, P4-
RT di(adenosine)tetraphosphate.";
RL Submitted (DEC-2005) to the PDB data bank.
RN [11]
RP VARIANT HAAKD CYS-164.
RX PubMed=9432020; DOI=10.1046/j.1365-2141.1997.4953299.x;
RA Qualtieri A., Pedace V., Bisconte M.G., Bria M., Gulino B.,
RA Andreoli V., Brancati C.;
RT "Severe erythrocyte adenylate kinase deficiency due to homozygous
RT A-->G substitution at codon 164 of human AK1 gene associated with
RT chronic haemolytic anaemia.";
RL Br. J. Haematol. 99:770-776(1997).
RN [12]
RP VARIANTS HAAKD ARG-40; ARG-64 AND ASP-140 DEL.
RX PubMed=12649162; DOI=10.1182/blood-2002-07-2288;
RA Corrons J.-L., Garcia E., Tusell J.J., Varughese K.I., West C.,
RA Beutler E.;
RT "Red cell adenylate kinase deficiency: molecular study of 3 new
RT mutations (118G>A, 190G>A, and GAC deletion) associated with
RT hereditary nonspherocytic hemolytic anemia.";
RL Blood 102:353-356(2003).
CC -!- FUNCTION: Catalyzes the reversible transfer of the terminal
CC phosphate group between ATP and AMP. Also displays broad
CC nucleoside diphosphate kinase activity. Plays an important role in
CC cellular energy homeostasis and in adenine nucleotide metabolism.
CC -!- CATALYTIC ACTIVITY: ATP + AMP = 2 ADP.
CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP +
CC nucleoside triphosphate.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and
CC two small peripheral domains, NMPbind and LID, which undergo
CC movements during catalysis. The LID domain closes over the site of
CC phosphoryl transfer upon ATP binding. Assembling and dissambling
CC the active center during each catalytic cycle provides an
CC effective means to prevent ATP hydrolysis.
CC -!- POLYMORPHISM: This enzyme represents the most common of at least
CC five alleles.
CC -!- DISEASE: Hemolytic anemia due to adenylate kinase deficiency
CC (HAAKD) [MIM:612631]: A disease characterized by hemolytic anemia
CC and undetectable erythrocyte adenylate kinase activity. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. AK1 subfamily.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Adenylate kinase entry;
CC URL="http://en.wikipedia.org/wiki/Adenylate_kinase";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; J04809; AAA51686.1; -; Genomic_DNA.
DR EMBL; AB021871; BAA78534.1; -; mRNA.
DR EMBL; BT019580; AAV38387.1; -; mRNA.
DR EMBL; BC001116; AAH01116.1; -; mRNA.
DR PIR; A33508; KIHUA.
DR RefSeq; NP_000467.1; NM_000476.2.
DR RefSeq; XP_005251844.1; XM_005251787.1.
DR UniGene; Hs.175473; -.
DR PDB; 1Z83; X-ray; 1.90 A; A/B/C=1-193.
DR PDB; 2C95; X-ray; 1.71 A; A/B=1-193.
DR PDBsum; 1Z83; -.
DR PDBsum; 2C95; -.
DR ProteinModelPortal; P00568; -.
DR SMR; P00568; 1-193.
DR IntAct; P00568; 1.
DR STRING; 9606.ENSP00000362249; -.
DR PhosphoSite; P00568; -.
DR DMDM; 20178288; -.
DR OGP; P00568; -.
DR REPRODUCTION-2DPAGE; IPI00018342; -.
DR UCD-2DPAGE; P00568; -.
DR PaxDb; P00568; -.
DR PRIDE; P00568; -.
DR DNASU; 203; -.
DR Ensembl; ENST00000373156; ENSP00000362249; ENSG00000106992.
DR Ensembl; ENST00000373176; ENSP00000362271; ENSG00000106992.
DR GeneID; 203; -.
DR KEGG; hsa:203; -.
DR UCSC; uc004bsm.4; human.
DR CTD; 203; -.
DR GeneCards; GC09M130628; -.
DR HGNC; HGNC:361; AK1.
DR HPA; CAB009893; -.
DR HPA; HPA006456; -.
DR MIM; 103000; gene.
DR MIM; 612631; phenotype.
DR neXtProt; NX_P00568; -.
DR Orphanet; 86817; Hemolytic anemia due to adenylate kinase deficiency.
DR PharmGKB; PA24655; -.
DR eggNOG; COG0563; -.
DR HOGENOM; HOG000238771; -.
DR HOVERGEN; HBG108060; -.
DR KO; K00939; -.
DR OrthoDB; EOG7060S3; -.
DR PhylomeDB; P00568; -.
DR BRENDA; 2.7.4.3; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00568; -.
DR EvolutionaryTrace; P00568; -.
DR GenomeRNAi; 203; -.
DR NextBio; 808; -.
DR PRO; PR:P00568; -.
DR ArrayExpress; P00568; -.
DR Bgee; P00568; -.
DR CleanEx; HS_AK1; -.
DR Genevestigator; P00568; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001520; C:outer dense fiber; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0036126; C:sperm flagellum; IEA:Ensembl.
DR GO; GO:0004017; F:adenylate kinase activity; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; IEA:InterPro.
DR GO; GO:0007050; P:cell cycle arrest; IEA:Ensembl.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 1; -.
DR HAMAP; MF_03171; Adenylate_kinase_AK1; 1; -.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR028582; AK1.
DR InterPro; IPR006267; AK1/5.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 1.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01360; aden_kin_iso1; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disease mutation;
KW Hereditary hemolytic anemia; Kinase; Nucleotide-binding; Polymorphism;
KW Reference proteome; Transferase.
FT CHAIN 1 194 Adenylate kinase isoenzyme 1.
FT /FTId=PRO_0000158910.
FT NP_BIND 18 23 ATP.
FT NP_BIND 65 67 AMP.
FT NP_BIND 94 97 AMP.
FT REGION 38 67 NMPbind.
FT REGION 131 141 LID.
FT BINDING 39 39 AMP.
FT BINDING 44 44 AMP.
FT BINDING 101 101 AMP.
FT BINDING 132 132 ATP.
FT BINDING 138 138 AMP.
FT BINDING 149 149 AMP.
FT BINDING 177 177 ATP; via carbonyl oxygen.
FT MOD_RES 1 1 N-acetylmethionine.
FT VARIANT 40 40 G -> R (in HAAKD).
FT /FTId=VAR_055337.
FT VARIANT 64 64 G -> R (in HAAKD).
FT /FTId=VAR_055338.
FT VARIANT 123 123 E -> Q (in dbSNP:rs8192462).
FT /FTId=VAR_034046.
FT VARIANT 128 128 R -> W (in HAAKD; dbSNP:rs28930974).
FT /FTId=VAR_004021.
FT VARIANT 140 140 Missing (in HAAKD).
FT /FTId=VAR_055339.
FT VARIANT 164 164 Y -> C (in HAAKD).
FT /FTId=VAR_055340.
FT CONFLICT 9 9 K -> N (in Ref. 5; AAH01116).
FT CONFLICT 127 127 Q -> R (in Ref. 1; AA sequence).
FT CONFLICT 181 181 S -> E (in Ref. 1; AA sequence).
FT HELIX 1 5
FT STRAND 10 15
FT HELIX 21 32
FT STRAND 35 38
FT HELIX 39 48
FT HELIX 52 62
FT HELIX 69 83
FT TURN 84 86
FT STRAND 90 94
FT HELIX 99 108
FT STRAND 113 119
FT HELIX 122 133
FT STRAND 135 137
FT HELIX 139 141
FT HELIX 143 156
FT HELIX 158 167
FT STRAND 170 174
FT HELIX 179 193
SQ SEQUENCE 194 AA; 21635 MW; 95EC5AAA92D1F00F CRC64;
MEEKLKKTKI IFVVGGPGSG KGTQCEKIVQ KYGYTHLSTG DLLRSEVSSG SARGKKLSEI
MEKGQLVPLE TVLDMLRDAM VAKVNTSKGF LIDGYPREVQ QGEEFERRIG QPTLLLYVDA
GPETMTQRLL KRGETSGRVD DNEETIKKRL ETYYKATEPV IAFYEKRGIV RKVNAEGSVD
SVFSQVCTHL DALK
//
ID KAD1_HUMAN Reviewed; 194 AA.
AC P00568; Q9BVK9; Q9UQC7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-APR-2002, sequence version 3.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Adenylate kinase isoenzyme 1;
DE Short=AK 1;
DE EC=2.7.4.3;
DE EC=2.7.4.6;
DE AltName: Full=ATP-AMP transphosphorylase 1;
DE AltName: Full=ATP:AMP phosphotransferase;
DE AltName: Full=Adenylate monophosphate kinase;
DE AltName: Full=Myokinase;
GN Name=AK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Skeletal muscle;
RX PubMed=183954; DOI=10.1111/j.1432-1033.1976.tb10787.x;
RA von Zabern I., Wittmann-Liebold B., Untucht-Grau R., Schirmer R.H.,
RA Pai E.F.;
RT "Primary and tertiary structure of the principal human adenylate
RT kinase.";
RL Eur. J. Biochem. 68:281-290(1976).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HAAKD TRP-128.
RX PubMed=2542324;
RA Matsuura S., Igarashi M., Tanizawa Y., Yamada M., Kishi F., Kajii T.,
RA Fujii H., Miwa S., Sakurai M., Nakazawa A.;
RT "Human adenylate kinase deficiency associated with hemolytic anemia. A
RT single base substitution affecting solubility and catalytic activity
RT of the cytosolic adenylate kinase.";
RL J. Biol. Chem. 264:10148-10155(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RA Noma T.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 10-21; 32-44; 64-77; 89-97; 108-128; 156-166 AND
RP 172-194, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
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.,
RA Buerckstuemmer T., 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 [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23416111; DOI=10.1016/j.biocel.2013.02.004;
RA Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.;
RT "The human adenylate kinase 9 is a nucleoside mono- and diphosphate
RT kinase.";
RL Int. J. Biochem. Cell Biol. 45:925-931(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE
RP ANALOG AP5A.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human AK1A in complex with AP5A.";
RL Submitted (MAR-2007) to the PDB data bank.
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEX WITH BI-SUBSTRATE
RP ANALOG AP4A.
RG Structural genomics consortium (SGC);
RT "Structure of adenylate kinase 1 in complex with P1, P4-
RT di(adenosine)tetraphosphate.";
RL Submitted (DEC-2005) to the PDB data bank.
RN [11]
RP VARIANT HAAKD CYS-164.
RX PubMed=9432020; DOI=10.1046/j.1365-2141.1997.4953299.x;
RA Qualtieri A., Pedace V., Bisconte M.G., Bria M., Gulino B.,
RA Andreoli V., Brancati C.;
RT "Severe erythrocyte adenylate kinase deficiency due to homozygous
RT A-->G substitution at codon 164 of human AK1 gene associated with
RT chronic haemolytic anaemia.";
RL Br. J. Haematol. 99:770-776(1997).
RN [12]
RP VARIANTS HAAKD ARG-40; ARG-64 AND ASP-140 DEL.
RX PubMed=12649162; DOI=10.1182/blood-2002-07-2288;
RA Corrons J.-L., Garcia E., Tusell J.J., Varughese K.I., West C.,
RA Beutler E.;
RT "Red cell adenylate kinase deficiency: molecular study of 3 new
RT mutations (118G>A, 190G>A, and GAC deletion) associated with
RT hereditary nonspherocytic hemolytic anemia.";
RL Blood 102:353-356(2003).
CC -!- FUNCTION: Catalyzes the reversible transfer of the terminal
CC phosphate group between ATP and AMP. Also displays broad
CC nucleoside diphosphate kinase activity. Plays an important role in
CC cellular energy homeostasis and in adenine nucleotide metabolism.
CC -!- CATALYTIC ACTIVITY: ATP + AMP = 2 ADP.
CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP +
CC nucleoside triphosphate.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and
CC two small peripheral domains, NMPbind and LID, which undergo
CC movements during catalysis. The LID domain closes over the site of
CC phosphoryl transfer upon ATP binding. Assembling and dissambling
CC the active center during each catalytic cycle provides an
CC effective means to prevent ATP hydrolysis.
CC -!- POLYMORPHISM: This enzyme represents the most common of at least
CC five alleles.
CC -!- DISEASE: Hemolytic anemia due to adenylate kinase deficiency
CC (HAAKD) [MIM:612631]: A disease characterized by hemolytic anemia
CC and undetectable erythrocyte adenylate kinase activity. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the adenylate kinase family. AK1 subfamily.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Adenylate kinase entry;
CC URL="http://en.wikipedia.org/wiki/Adenylate_kinase";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; J04809; AAA51686.1; -; Genomic_DNA.
DR EMBL; AB021871; BAA78534.1; -; mRNA.
DR EMBL; BT019580; AAV38387.1; -; mRNA.
DR EMBL; BC001116; AAH01116.1; -; mRNA.
DR PIR; A33508; KIHUA.
DR RefSeq; NP_000467.1; NM_000476.2.
DR RefSeq; XP_005251844.1; XM_005251787.1.
DR UniGene; Hs.175473; -.
DR PDB; 1Z83; X-ray; 1.90 A; A/B/C=1-193.
DR PDB; 2C95; X-ray; 1.71 A; A/B=1-193.
DR PDBsum; 1Z83; -.
DR PDBsum; 2C95; -.
DR ProteinModelPortal; P00568; -.
DR SMR; P00568; 1-193.
DR IntAct; P00568; 1.
DR STRING; 9606.ENSP00000362249; -.
DR PhosphoSite; P00568; -.
DR DMDM; 20178288; -.
DR OGP; P00568; -.
DR REPRODUCTION-2DPAGE; IPI00018342; -.
DR UCD-2DPAGE; P00568; -.
DR PaxDb; P00568; -.
DR PRIDE; P00568; -.
DR DNASU; 203; -.
DR Ensembl; ENST00000373156; ENSP00000362249; ENSG00000106992.
DR Ensembl; ENST00000373176; ENSP00000362271; ENSG00000106992.
DR GeneID; 203; -.
DR KEGG; hsa:203; -.
DR UCSC; uc004bsm.4; human.
DR CTD; 203; -.
DR GeneCards; GC09M130628; -.
DR HGNC; HGNC:361; AK1.
DR HPA; CAB009893; -.
DR HPA; HPA006456; -.
DR MIM; 103000; gene.
DR MIM; 612631; phenotype.
DR neXtProt; NX_P00568; -.
DR Orphanet; 86817; Hemolytic anemia due to adenylate kinase deficiency.
DR PharmGKB; PA24655; -.
DR eggNOG; COG0563; -.
DR HOGENOM; HOG000238771; -.
DR HOVERGEN; HBG108060; -.
DR KO; K00939; -.
DR OrthoDB; EOG7060S3; -.
DR PhylomeDB; P00568; -.
DR BRENDA; 2.7.4.3; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00568; -.
DR EvolutionaryTrace; P00568; -.
DR GenomeRNAi; 203; -.
DR NextBio; 808; -.
DR PRO; PR:P00568; -.
DR ArrayExpress; P00568; -.
DR Bgee; P00568; -.
DR CleanEx; HS_AK1; -.
DR Genevestigator; P00568; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001520; C:outer dense fiber; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0036126; C:sperm flagellum; IEA:Ensembl.
DR GO; GO:0004017; F:adenylate kinase activity; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; IEA:InterPro.
DR GO; GO:0007050; P:cell cycle arrest; IEA:Ensembl.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 1; -.
DR HAMAP; MF_03171; Adenylate_kinase_AK1; 1; -.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR028582; AK1.
DR InterPro; IPR006267; AK1/5.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 1.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01360; aden_kin_iso1; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disease mutation;
KW Hereditary hemolytic anemia; Kinase; Nucleotide-binding; Polymorphism;
KW Reference proteome; Transferase.
FT CHAIN 1 194 Adenylate kinase isoenzyme 1.
FT /FTId=PRO_0000158910.
FT NP_BIND 18 23 ATP.
FT NP_BIND 65 67 AMP.
FT NP_BIND 94 97 AMP.
FT REGION 38 67 NMPbind.
FT REGION 131 141 LID.
FT BINDING 39 39 AMP.
FT BINDING 44 44 AMP.
FT BINDING 101 101 AMP.
FT BINDING 132 132 ATP.
FT BINDING 138 138 AMP.
FT BINDING 149 149 AMP.
FT BINDING 177 177 ATP; via carbonyl oxygen.
FT MOD_RES 1 1 N-acetylmethionine.
FT VARIANT 40 40 G -> R (in HAAKD).
FT /FTId=VAR_055337.
FT VARIANT 64 64 G -> R (in HAAKD).
FT /FTId=VAR_055338.
FT VARIANT 123 123 E -> Q (in dbSNP:rs8192462).
FT /FTId=VAR_034046.
FT VARIANT 128 128 R -> W (in HAAKD; dbSNP:rs28930974).
FT /FTId=VAR_004021.
FT VARIANT 140 140 Missing (in HAAKD).
FT /FTId=VAR_055339.
FT VARIANT 164 164 Y -> C (in HAAKD).
FT /FTId=VAR_055340.
FT CONFLICT 9 9 K -> N (in Ref. 5; AAH01116).
FT CONFLICT 127 127 Q -> R (in Ref. 1; AA sequence).
FT CONFLICT 181 181 S -> E (in Ref. 1; AA sequence).
FT HELIX 1 5
FT STRAND 10 15
FT HELIX 21 32
FT STRAND 35 38
FT HELIX 39 48
FT HELIX 52 62
FT HELIX 69 83
FT TURN 84 86
FT STRAND 90 94
FT HELIX 99 108
FT STRAND 113 119
FT HELIX 122 133
FT STRAND 135 137
FT HELIX 139 141
FT HELIX 143 156
FT HELIX 158 167
FT STRAND 170 174
FT HELIX 179 193
SQ SEQUENCE 194 AA; 21635 MW; 95EC5AAA92D1F00F CRC64;
MEEKLKKTKI IFVVGGPGSG KGTQCEKIVQ KYGYTHLSTG DLLRSEVSSG SARGKKLSEI
MEKGQLVPLE TVLDMLRDAM VAKVNTSKGF LIDGYPREVQ QGEEFERRIG QPTLLLYVDA
GPETMTQRLL KRGETSGRVD DNEETIKKRL ETYYKATEPV IAFYEKRGIV RKVNAEGSVD
SVFSQVCTHL DALK
//
MIM
103000
*RECORD*
*FIELD* NO
103000
*FIELD* TI
*103000 ADENYLATE KINASE 1; AK1
;;ADENYLATE KINASE, SOLUBLE
*FIELD* TX
DESCRIPTION
read more
Adenylate kinase (EC 2.7.4.3) is a ubiquitous monomeric enzyme that
catalyzes the reversible conversion of MgATP plus AMP to MgADP plus ADP
and contributes to homeostasis of the adenine nucleotide composition in
the cell (Matsuura et al., 1989).
CLONING
By screening a human genomic library with chicken Ak1 cDNA, Matsuura et
al. (1989) cloned the AK1 gene. The deduced protein contains 194 amino
acids. Northern blot analysis of human skeletal muscle RNA revealed
transcripts of 0.9 and 2.5 kb that differed in their 3-prime tails.
GENE STRUCTURE
Matsuura et al. (1989) determined that the AK1 gene spans 12 kb and has
7 exons. The 5-prime flanking region contains a TATA box and 3 putative
SP1 (189906)-binding sites within a GC-rich region, but it has no
typical CAAT box. The 3-prime region contains 3 canonical
polyadenylation signals. Alu sequences are located in the large intron 5
and in the noncoding region of exon 7.
MAPPING
Rapley et al. (1967) concluded that the AK locus is linked to the ABO
(110300) locus with a recombination value of about 0.20. Schleutermann
et al. (1969) found that the nail-patella syndrome locus (NPS1; 161200)
and the AK locus are closely linked. No recombination was found in 53
opportunities. Fenger and Sorensen (1975) found a 1.33 to 1 ratio for
the female to male recombination fractions between ABO and AK, but the
difference between the recombination fractions was not significantly
different from zero. All published data combined showed the most likely
recombination fraction to be about 14%. Westerveld et al. (1976) found
evidence that the AK locus assigned to chromosome 9 is the AK1 locus, or
so-called red cell AK.
In an early instance of deletion mapping, Ferguson-Smith et al. (1976)
localized the ABO-NPS1-AK1 linkage group to 9q34 by regional assignment
of AK1 in studies of a chromosome deletion. Cook et al. (1978) collated
evidence that ABO-AK1 lie in band 9q34. They could exclude MNSs, GPT,
and Gc from chromosome 9. AK1 is proximal to the break in the
Philadelphia chromosome rearrangement (Geurts van Kessel et al., 1982).
On the basis of a chromosome 9 aberration, an inverted paracentric
insertion, inv ins(9)(q22.1q34.3q34.1), Allderdice et al. (1986)
concluded that AK1 is located in 9q34.1-q34.3. Since AK1 is in 9q34 and
is proximal to the breakpoint that creates the Philadelphia chromosome
in chronic myeloid leukemia, located in band 9q34.1, AK1 and probably
the linked ABO locus may be in the proximal part of 9q34.1.
MOLECULAR GENETICS
Fildes and Harris (1966) found electrophoretic variation in red cells
and defined 3 phenotypes, designated AK1, AK2-1 and AK2. All of the 141
children of 2 AK1 parents (62 such matings) were also AK1. Among the 136
children of AK1 by AK2-1 matings, 72 were AK1 and 64 AK2-1. AK1 and AK2
persons were thought to be homozygotes for a 2-allele system and AK2-1
persons heterozygotes. The frequency of the rarer AK2 allele was about
0.05 in the English and about 1 in 400 persons would be expected to be
homozygous for this allele. Survey and family data were consistent.
Singer and Brock (1971) identified a probably silent allele at the AK
locus.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
In a patient with hemolytic anemia and adenylate kinase deficiency
(612631), Matsuura et al. (1989) identified an arg128-to-trp mutation
(103000.0001) in the AK1 gene.
In 2 sibs of Italian origin with mild chronic hemolytic anemia,
psychomotor impairment, and undetectable adenylate kinase activity,
Bianchi et al. (1999) identified an arg107-to-ter mutation (103000.0002)
in the AK1 gene.
ANIMAL MODEL
Janssen et al. (2000) studied energy homeostasis in muscle of Ak1 null
mice. Disruption of Ak1 decreased the potential of myofibers to sustain
nucleotide ratios despite upregulated glycolytic, guanylate, and
creatine kinase phosphotransfer pathways. Maintained contraction of
Ak1-deficient muscles was associated with reduced energy efficiency that
was aggravated by hypoxic stress.
HISTORY
Cavalli-Sforza et al. (1979) presented evidence for linkage of
transcobalamin II and adenylate kinase (lod score 1.78 at theta 0.139).
This was not subsequently confirmed.
In a patient with deletion 9q32-qter secondary to a balanced maternal
translocation, Zuffardi et al. (1989) found normal levels of adenylate
kinase. Comparing this to previously published data, the authors
concluded that the AK1 locus may be situated in 9q32.
*FIELD* AV
.0001
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, ARG128TRP
In a patient with hemolytic anemia and adenylate kinase deficiency
(612631), Matsuura et al. (1989) demonstrated a transition (C-to-T) in
exon 6 which resulted in an arg-to-trp (CGG-to-TGG) substitution at
residue 128 of AK1. Mutant chicken AK1, produced by introducing an
arg-to-trp substitution at the same position by
oligodeoxynucleotide-directed mutagenesis, showed reduced catalytic
activity as well as decreased solubility when expressed in E. coli.
.0002
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, ARG107TER
Bianchi et al. (1999) described 2 sibs of Italian origin with mild
chronic hemolytic anemia, psychomotor impairment, and undetectable
adenylate kinase activity (612631). The other red cell enzyme activities
were normal except for a slight decrease in phosphofructokinase (see
PFKM; 610681). Both sibs showed increased levels of 2,3-DPG. The parents
were not consanguineous and displayed intermediate AK values. The
sequence of complete erythrocyte AK1 cDNA showed homozygosity for a
nonsense mutation at codon 107: CGA (arg) to TGA (stop). The mutation
resulted in a truncated protein of 107 amino acids in comparison with
the normal 194. Moreover, a 37-bp deletion in the first part of exon 6
(nucleotides 326-362 of the cDNA sequence) was detectable in one allele.
Because this deletion was localized after the stop codon, the authors
thought that it would not have a further effect on the structure of the
enzyme. The new variant was named AK Fidenza, from the origin of the
patients.
.0003
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, TYR164CYS
In an Italian child with hemolytic anemia and undetectable erythrocyte
adenylate kinase activity (612631), Qualtieri et al. (1997) identified
homozygosity for an A-to-G transition in exon 6 of the AK1 gene,
resulting in a tyr164-to-cys substitution. Her parents and brother were
heterozygous for the mutation and had 50% normal AK1 activity.
.0004
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, GLY40ARG
In a Spanish boy with chronic nonspherocytic hemolytic anemia and severe
red blood cell adenylate kinase deficiency (612631), Corrons et al.
(2003) identified compound heterozygosity for 2 mutations in the AK1
gene: a 118G-A transition resulting in a gly40-to-arg (G40R)
substitution, and a 190G-A transition resulting in a gly64-to-arg (G64R)
substitution (103000.0005). The boy exhibited a neonatal icterus and
splenomegaly and required blood transfusions until the age of 2 years.
.0005
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, GLY64ARG
See 103000.0004 and Corrons et al. (2003).
.0006
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, 3-BP DEL, 498GAC
In a white American infant with chronic nonspherocytic hemolytic anemia
and severe red blood cell adenylate kinase deficiency (612631), whose
parents were first cousins, Corrons et al. (2003) identified
homozygosity for an in-frame deletion (GAC) at nucleotide 498 or 501,
predicting deletion of either aspartic acid 140 or 141.
.0007
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, 1-BP DEL, 138G
In a 3-year-old girl of southern Italian origin with a history of severe
hemolytic anemia and low adenylate kinase activity (22% of normal)
(612631), Fermo et al. (2004) identified homozygosity for a 1-bp
deletion (138delG), causing a frameshift and a premature stop at codon
91.
*FIELD* SA
Bowman et al. (1967); Brock (1970); Mohandas et al. (1979); Povey
et al. (1976); Seger et al. (1978); Weitkamp et al. (1969)
*FIELD* RF
1. Allderdice, P. W.; Kaita, H.; Lewis, M.; McAlpine, P. J.; Wong,
P.; Anderson, J.; Giblett, E. R.: Segregation of marker loci in families
with an inherited paracentric insertion of chromosome 9. Am. J. Hum.
Genet. 39: 612-617, 1986.
2. Bianchi, P.; Zappa, M.; Bredi, E.; Vercellati, C.; Pelissero, G.;
Barraco, F.; Zanella, A.: A case of complete adenylate kinase deficiency
due to a nonsense mutation in AK-1 gene (arg107-to-stop, CGA-to-TGA)
associated with chronic haemolytic anaemia. Brit. J. Haemat. 105:
75-79, 1999.
3. Bowman, J. E.; Frischer, H.; Ajmar, F.; Carson, P. E.; Gower, M.
K.: Population, family and biochemical investigation of human adenylate
kinase polymorphism. Nature 214: 1156-1158, 1967.
4. Brock, D. J. H.: Evidence against a common subunit in adenylate
kinase and pyruvate kinase. Humangenetik 10: 30-34, 1970.
5. Cavalli-Sforza, L. L.; King, M. C.; Go, R. C. P.; Namboodiri, K.
K.; Lynch, H. T.; Wong, L.; Kaplan, E. B.; Elston, R. C.: Possible
linkage between transcobalamin II (TC II) and adenylate kinase (AK).
(Abstract) Cytogenet. Cell Genet. 25: 140-141, 1979.
6. Cook, P. J. L.; Robson, E. B.; Buckton, K. E.; Slaughter, C. A.;
Gray, J. E.; Blank, C. E.; James, F. E.; Ridler, M. A. C.; Insley,
J.; Hulten, M.: Segregation of ABO, AK(1) and ACONs in families with
abnormalities of chromosome 9. Ann. Hum. Genet. 41: 365-377, 1978.
7. Corrons, J.-L. V.; Garcia, E.; Tusell, J. J.; Varughese, K. I.;
West, C.; Beutler, E.: Red cell adenylate kinase deficiency: molecular
study of 3 new mutations (118G-A, 190G-A, and GAC deletion) associated
with hereditary nonspherocytic hemolytic anemia. Blood 102: 353-356,
2003.
8. Fenger, K.; Sorensen, S. A.: Evaluation of a possible sex difference
in recombination for the ABO-AK linkage. Am. J. Hum. Genet. 27:
784-788, 1975.
9. Ferguson-Smith, M. A.; Aitken, D. A.; Turleau, C.; de Grouchy,
J.: Localisation of the human ABO: Np-1: AK-1 linkage group by regional
assignment of AK-1 to 9q34. Hum. Genet. 34: 35-43, 1976.
10. Fermo, E.; Bianchi, P.; Vercellati, C.; Micheli, S.; Marcello,
A. P.; Portaleone, D.; Zanella, A.: A new variant of adenylate kinase
(delG138) associated with severe hemolytic anemia. Blood Cells Molec.
Dis. 33: 146-149, 2004.
11. Fildes, R. A.; Harris, H.: Genetically determined variation of
adenylate kinase in man. Nature 209: 261-262, 1966.
12. Geurts van Kessel, A. H. M.; Hagemeijer, A.; Westerveld, A.; Meera
Khan, P.; de Groot, P. G.; Pearson, P. L.: Characterization of chromosomal
abnormalities in chronic myeloid leukemia using somatic cell hybrids.
(Abstract) Cytogenet. Cell Genet. 32: 280 only, 1982.
13. Janssen, E.; Dzeja, P. P.; Oerlemans, F.; Simonetti, A. W.; Heerschap,
A.; de Haan, A.; Rush, P. S.; Terjung, R. R.; Wieringa, B.; Terzic,
A.: Adenylate kinase 1 gene deletion disrupts muscle energetic economy
despite metabolic rearrangement. EMBO J. 19: 6371-6381, 2000.
14. Matsuura, S.; Igarashi, M.; Tanizawa, Y.; Yamada, M.; Kishi, F.;
Kajii, T.; Fujii, H.; Miwa, S.; Sakurai, M.; Nakazawa, A.: Human
adenylate kinase deficiency associated with hemolytic anemia: a single
base substitution affecting solubility and catalytic activity of the
cytosolic adenylate kinase. J. Biol. Chem. 264: 10148-10155, 1989.
15. Mohandas, T.; Sparkes, R. S.; Sparkes, M. C.; Shulkin, J. D.;
Toomey, K. E.; Funderburk, S. J.: Regional localization of human
gene loci on chromosome 9: studies of somatic cell hybrids containing
human translocations. Am. J. Hum. Genet. 31: 586-600, 1979.
16. Povey, S.; Slaughter, C. A.; Wilson, D. E.; Gormley, I. P.; Buckton,
K. E.; Perry, P.; Bobrow, M.: Evidence for the assignment of loci
AK 1, AK 3 and ACON to chromosome 9 in man. Ann. Hum. Genet. 39:
413-422, 1976.
17. Qualtieri, A.; Pedace, V.; Bisconte, M. G.; Bria, M.; Gulino,
B.; Andreoli, V.; Brancati, C.: Severe erythrocyte adenylate kinase
deficiency due to homozygous A-to-G substitution at codon 164 of human
AK1 gene associated with chronic haemolytic anaemia. Brit. J. Haemat. 99:
770-776, 1997.
18. Rapley, S.; Robson, E. B.; Harris, H.; Smith, S. M.: Data on
the incidence, segregation and linkage relations of the adenylate
kinase (AK) polymorphism. Ann. Hum. Genet. 31: 237-242, 1967.
19. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
20. Schleutermann, D. A.; Bias, W. B.; Murdoch, J. L.; McKusick, V.
A.: Linkage of the loci for the nail-patella syndrome and adenylate
kinase. Am. J. Hum. Genet. 21: 606-630, 1969.
21. Seger, J.; Tchen, P.; Feingold, N.; Grenand, F.; Bois, E.: Homozygosity
of adenylate kinase allele 3: two cases. Hum. Genet. 43: 337-339,
1978.
22. Singer, J. D.; Brock, D. J.: Half-normal adenylate kinase activity
in three generations. Ann. Hum. Genet. 35: 109-114, 1971.
23. Weitkamp, L. R.; Sing, C. F.; Shreffler, D. C.; Guttormsen, S.
A.: The genetic linkage relations of adenylate kinase: further data
on the ABO-AK linkage group. Am. J. Hum. Genet. 21: 600-605, 1969.
24. Westerveld, A.; Jongsma, A. P. M.; Meera Khan, P.; Van Someren,
H.; Bootsma, D.: Assignment of the AK(1): Np: AKO linkage group to
human chromosome 9. Proc. Nat. Acad. Sci. 73: 895-899, 1976.
25. Zuffardi, O.; Caiulo, A.; Maraschio, P.; Tupler, R.; Bianchi,
E.; Amisano, P.; Beluffi, G.; Moratti, R.; Liguri, G.: Regional assignment
of the loci for adenylate kinase to 9q32 and for alpha(1)-acid glycoprotein
to 9q31-q32: a locus for Goltz syndrome in region 9q32-qter? Hum.
Genet. 82: 17-19, 1989.
*FIELD* CN
Patricia A. Hartz - updated: 2/26/2009
Carol A. Bocchini - updated: 2/18/2009
Victor A. McKusick - updated: 10/10/2003
Patricia A. Hartz - updated: 6/11/2003
Victor A. McKusick - updated: 6/3/1999
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 03/03/2009
mgross: 2/27/2009
terry: 2/26/2009
terry: 2/18/2009
carol: 2/18/2009
carol: 2/17/2009
terry: 1/7/2009
ckniffin: 3/8/2007
ckniffin: 6/1/2004
mgross: 3/17/2004
tkritzer: 10/21/2003
terry: 10/10/2003
mgross: 6/11/2003
kayiaros: 7/13/1999
carol: 6/15/1999
jlewis: 6/14/1999
jlewis: 6/9/1999
terry: 6/3/1999
terry: 4/29/1999
alopez: 5/8/1998
psherman: 4/15/1998
terry: 8/30/1994
mimadm: 3/11/1994
carol: 5/12/1993
supermim: 3/16/1992
carol: 1/27/1992
carol: 10/3/1991
*RECORD*
*FIELD* NO
103000
*FIELD* TI
*103000 ADENYLATE KINASE 1; AK1
;;ADENYLATE KINASE, SOLUBLE
*FIELD* TX
DESCRIPTION
read more
Adenylate kinase (EC 2.7.4.3) is a ubiquitous monomeric enzyme that
catalyzes the reversible conversion of MgATP plus AMP to MgADP plus ADP
and contributes to homeostasis of the adenine nucleotide composition in
the cell (Matsuura et al., 1989).
CLONING
By screening a human genomic library with chicken Ak1 cDNA, Matsuura et
al. (1989) cloned the AK1 gene. The deduced protein contains 194 amino
acids. Northern blot analysis of human skeletal muscle RNA revealed
transcripts of 0.9 and 2.5 kb that differed in their 3-prime tails.
GENE STRUCTURE
Matsuura et al. (1989) determined that the AK1 gene spans 12 kb and has
7 exons. The 5-prime flanking region contains a TATA box and 3 putative
SP1 (189906)-binding sites within a GC-rich region, but it has no
typical CAAT box. The 3-prime region contains 3 canonical
polyadenylation signals. Alu sequences are located in the large intron 5
and in the noncoding region of exon 7.
MAPPING
Rapley et al. (1967) concluded that the AK locus is linked to the ABO
(110300) locus with a recombination value of about 0.20. Schleutermann
et al. (1969) found that the nail-patella syndrome locus (NPS1; 161200)
and the AK locus are closely linked. No recombination was found in 53
opportunities. Fenger and Sorensen (1975) found a 1.33 to 1 ratio for
the female to male recombination fractions between ABO and AK, but the
difference between the recombination fractions was not significantly
different from zero. All published data combined showed the most likely
recombination fraction to be about 14%. Westerveld et al. (1976) found
evidence that the AK locus assigned to chromosome 9 is the AK1 locus, or
so-called red cell AK.
In an early instance of deletion mapping, Ferguson-Smith et al. (1976)
localized the ABO-NPS1-AK1 linkage group to 9q34 by regional assignment
of AK1 in studies of a chromosome deletion. Cook et al. (1978) collated
evidence that ABO-AK1 lie in band 9q34. They could exclude MNSs, GPT,
and Gc from chromosome 9. AK1 is proximal to the break in the
Philadelphia chromosome rearrangement (Geurts van Kessel et al., 1982).
On the basis of a chromosome 9 aberration, an inverted paracentric
insertion, inv ins(9)(q22.1q34.3q34.1), Allderdice et al. (1986)
concluded that AK1 is located in 9q34.1-q34.3. Since AK1 is in 9q34 and
is proximal to the breakpoint that creates the Philadelphia chromosome
in chronic myeloid leukemia, located in band 9q34.1, AK1 and probably
the linked ABO locus may be in the proximal part of 9q34.1.
MOLECULAR GENETICS
Fildes and Harris (1966) found electrophoretic variation in red cells
and defined 3 phenotypes, designated AK1, AK2-1 and AK2. All of the 141
children of 2 AK1 parents (62 such matings) were also AK1. Among the 136
children of AK1 by AK2-1 matings, 72 were AK1 and 64 AK2-1. AK1 and AK2
persons were thought to be homozygotes for a 2-allele system and AK2-1
persons heterozygotes. The frequency of the rarer AK2 allele was about
0.05 in the English and about 1 in 400 persons would be expected to be
homozygous for this allele. Survey and family data were consistent.
Singer and Brock (1971) identified a probably silent allele at the AK
locus.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
In a patient with hemolytic anemia and adenylate kinase deficiency
(612631), Matsuura et al. (1989) identified an arg128-to-trp mutation
(103000.0001) in the AK1 gene.
In 2 sibs of Italian origin with mild chronic hemolytic anemia,
psychomotor impairment, and undetectable adenylate kinase activity,
Bianchi et al. (1999) identified an arg107-to-ter mutation (103000.0002)
in the AK1 gene.
ANIMAL MODEL
Janssen et al. (2000) studied energy homeostasis in muscle of Ak1 null
mice. Disruption of Ak1 decreased the potential of myofibers to sustain
nucleotide ratios despite upregulated glycolytic, guanylate, and
creatine kinase phosphotransfer pathways. Maintained contraction of
Ak1-deficient muscles was associated with reduced energy efficiency that
was aggravated by hypoxic stress.
HISTORY
Cavalli-Sforza et al. (1979) presented evidence for linkage of
transcobalamin II and adenylate kinase (lod score 1.78 at theta 0.139).
This was not subsequently confirmed.
In a patient with deletion 9q32-qter secondary to a balanced maternal
translocation, Zuffardi et al. (1989) found normal levels of adenylate
kinase. Comparing this to previously published data, the authors
concluded that the AK1 locus may be situated in 9q32.
*FIELD* AV
.0001
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, ARG128TRP
In a patient with hemolytic anemia and adenylate kinase deficiency
(612631), Matsuura et al. (1989) demonstrated a transition (C-to-T) in
exon 6 which resulted in an arg-to-trp (CGG-to-TGG) substitution at
residue 128 of AK1. Mutant chicken AK1, produced by introducing an
arg-to-trp substitution at the same position by
oligodeoxynucleotide-directed mutagenesis, showed reduced catalytic
activity as well as decreased solubility when expressed in E. coli.
.0002
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, ARG107TER
Bianchi et al. (1999) described 2 sibs of Italian origin with mild
chronic hemolytic anemia, psychomotor impairment, and undetectable
adenylate kinase activity (612631). The other red cell enzyme activities
were normal except for a slight decrease in phosphofructokinase (see
PFKM; 610681). Both sibs showed increased levels of 2,3-DPG. The parents
were not consanguineous and displayed intermediate AK values. The
sequence of complete erythrocyte AK1 cDNA showed homozygosity for a
nonsense mutation at codon 107: CGA (arg) to TGA (stop). The mutation
resulted in a truncated protein of 107 amino acids in comparison with
the normal 194. Moreover, a 37-bp deletion in the first part of exon 6
(nucleotides 326-362 of the cDNA sequence) was detectable in one allele.
Because this deletion was localized after the stop codon, the authors
thought that it would not have a further effect on the structure of the
enzyme. The new variant was named AK Fidenza, from the origin of the
patients.
.0003
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, TYR164CYS
In an Italian child with hemolytic anemia and undetectable erythrocyte
adenylate kinase activity (612631), Qualtieri et al. (1997) identified
homozygosity for an A-to-G transition in exon 6 of the AK1 gene,
resulting in a tyr164-to-cys substitution. Her parents and brother were
heterozygous for the mutation and had 50% normal AK1 activity.
.0004
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, GLY40ARG
In a Spanish boy with chronic nonspherocytic hemolytic anemia and severe
red blood cell adenylate kinase deficiency (612631), Corrons et al.
(2003) identified compound heterozygosity for 2 mutations in the AK1
gene: a 118G-A transition resulting in a gly40-to-arg (G40R)
substitution, and a 190G-A transition resulting in a gly64-to-arg (G64R)
substitution (103000.0005). The boy exhibited a neonatal icterus and
splenomegaly and required blood transfusions until the age of 2 years.
.0005
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, GLY64ARG
See 103000.0004 and Corrons et al. (2003).
.0006
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, 3-BP DEL, 498GAC
In a white American infant with chronic nonspherocytic hemolytic anemia
and severe red blood cell adenylate kinase deficiency (612631), whose
parents were first cousins, Corrons et al. (2003) identified
homozygosity for an in-frame deletion (GAC) at nucleotide 498 or 501,
predicting deletion of either aspartic acid 140 or 141.
.0007
ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
AK1, 1-BP DEL, 138G
In a 3-year-old girl of southern Italian origin with a history of severe
hemolytic anemia and low adenylate kinase activity (22% of normal)
(612631), Fermo et al. (2004) identified homozygosity for a 1-bp
deletion (138delG), causing a frameshift and a premature stop at codon
91.
*FIELD* SA
Bowman et al. (1967); Brock (1970); Mohandas et al. (1979); Povey
et al. (1976); Seger et al. (1978); Weitkamp et al. (1969)
*FIELD* RF
1. Allderdice, P. W.; Kaita, H.; Lewis, M.; McAlpine, P. J.; Wong,
P.; Anderson, J.; Giblett, E. R.: Segregation of marker loci in families
with an inherited paracentric insertion of chromosome 9. Am. J. Hum.
Genet. 39: 612-617, 1986.
2. Bianchi, P.; Zappa, M.; Bredi, E.; Vercellati, C.; Pelissero, G.;
Barraco, F.; Zanella, A.: A case of complete adenylate kinase deficiency
due to a nonsense mutation in AK-1 gene (arg107-to-stop, CGA-to-TGA)
associated with chronic haemolytic anaemia. Brit. J. Haemat. 105:
75-79, 1999.
3. Bowman, J. E.; Frischer, H.; Ajmar, F.; Carson, P. E.; Gower, M.
K.: Population, family and biochemical investigation of human adenylate
kinase polymorphism. Nature 214: 1156-1158, 1967.
4. Brock, D. J. H.: Evidence against a common subunit in adenylate
kinase and pyruvate kinase. Humangenetik 10: 30-34, 1970.
5. Cavalli-Sforza, L. L.; King, M. C.; Go, R. C. P.; Namboodiri, K.
K.; Lynch, H. T.; Wong, L.; Kaplan, E. B.; Elston, R. C.: Possible
linkage between transcobalamin II (TC II) and adenylate kinase (AK).
(Abstract) Cytogenet. Cell Genet. 25: 140-141, 1979.
6. Cook, P. J. L.; Robson, E. B.; Buckton, K. E.; Slaughter, C. A.;
Gray, J. E.; Blank, C. E.; James, F. E.; Ridler, M. A. C.; Insley,
J.; Hulten, M.: Segregation of ABO, AK(1) and ACONs in families with
abnormalities of chromosome 9. Ann. Hum. Genet. 41: 365-377, 1978.
7. Corrons, J.-L. V.; Garcia, E.; Tusell, J. J.; Varughese, K. I.;
West, C.; Beutler, E.: Red cell adenylate kinase deficiency: molecular
study of 3 new mutations (118G-A, 190G-A, and GAC deletion) associated
with hereditary nonspherocytic hemolytic anemia. Blood 102: 353-356,
2003.
8. Fenger, K.; Sorensen, S. A.: Evaluation of a possible sex difference
in recombination for the ABO-AK linkage. Am. J. Hum. Genet. 27:
784-788, 1975.
9. Ferguson-Smith, M. A.; Aitken, D. A.; Turleau, C.; de Grouchy,
J.: Localisation of the human ABO: Np-1: AK-1 linkage group by regional
assignment of AK-1 to 9q34. Hum. Genet. 34: 35-43, 1976.
10. Fermo, E.; Bianchi, P.; Vercellati, C.; Micheli, S.; Marcello,
A. P.; Portaleone, D.; Zanella, A.: A new variant of adenylate kinase
(delG138) associated with severe hemolytic anemia. Blood Cells Molec.
Dis. 33: 146-149, 2004.
11. Fildes, R. A.; Harris, H.: Genetically determined variation of
adenylate kinase in man. Nature 209: 261-262, 1966.
12. Geurts van Kessel, A. H. M.; Hagemeijer, A.; Westerveld, A.; Meera
Khan, P.; de Groot, P. G.; Pearson, P. L.: Characterization of chromosomal
abnormalities in chronic myeloid leukemia using somatic cell hybrids.
(Abstract) Cytogenet. Cell Genet. 32: 280 only, 1982.
13. Janssen, E.; Dzeja, P. P.; Oerlemans, F.; Simonetti, A. W.; Heerschap,
A.; de Haan, A.; Rush, P. S.; Terjung, R. R.; Wieringa, B.; Terzic,
A.: Adenylate kinase 1 gene deletion disrupts muscle energetic economy
despite metabolic rearrangement. EMBO J. 19: 6371-6381, 2000.
14. Matsuura, S.; Igarashi, M.; Tanizawa, Y.; Yamada, M.; Kishi, F.;
Kajii, T.; Fujii, H.; Miwa, S.; Sakurai, M.; Nakazawa, A.: Human
adenylate kinase deficiency associated with hemolytic anemia: a single
base substitution affecting solubility and catalytic activity of the
cytosolic adenylate kinase. J. Biol. Chem. 264: 10148-10155, 1989.
15. Mohandas, T.; Sparkes, R. S.; Sparkes, M. C.; Shulkin, J. D.;
Toomey, K. E.; Funderburk, S. J.: Regional localization of human
gene loci on chromosome 9: studies of somatic cell hybrids containing
human translocations. Am. J. Hum. Genet. 31: 586-600, 1979.
16. Povey, S.; Slaughter, C. A.; Wilson, D. E.; Gormley, I. P.; Buckton,
K. E.; Perry, P.; Bobrow, M.: Evidence for the assignment of loci
AK 1, AK 3 and ACON to chromosome 9 in man. Ann. Hum. Genet. 39:
413-422, 1976.
17. Qualtieri, A.; Pedace, V.; Bisconte, M. G.; Bria, M.; Gulino,
B.; Andreoli, V.; Brancati, C.: Severe erythrocyte adenylate kinase
deficiency due to homozygous A-to-G substitution at codon 164 of human
AK1 gene associated with chronic haemolytic anaemia. Brit. J. Haemat. 99:
770-776, 1997.
18. Rapley, S.; Robson, E. B.; Harris, H.; Smith, S. M.: Data on
the incidence, segregation and linkage relations of the adenylate
kinase (AK) polymorphism. Ann. Hum. Genet. 31: 237-242, 1967.
19. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
20. Schleutermann, D. A.; Bias, W. B.; Murdoch, J. L.; McKusick, V.
A.: Linkage of the loci for the nail-patella syndrome and adenylate
kinase. Am. J. Hum. Genet. 21: 606-630, 1969.
21. Seger, J.; Tchen, P.; Feingold, N.; Grenand, F.; Bois, E.: Homozygosity
of adenylate kinase allele 3: two cases. Hum. Genet. 43: 337-339,
1978.
22. Singer, J. D.; Brock, D. J.: Half-normal adenylate kinase activity
in three generations. Ann. Hum. Genet. 35: 109-114, 1971.
23. Weitkamp, L. R.; Sing, C. F.; Shreffler, D. C.; Guttormsen, S.
A.: The genetic linkage relations of adenylate kinase: further data
on the ABO-AK linkage group. Am. J. Hum. Genet. 21: 600-605, 1969.
24. Westerveld, A.; Jongsma, A. P. M.; Meera Khan, P.; Van Someren,
H.; Bootsma, D.: Assignment of the AK(1): Np: AKO linkage group to
human chromosome 9. Proc. Nat. Acad. Sci. 73: 895-899, 1976.
25. Zuffardi, O.; Caiulo, A.; Maraschio, P.; Tupler, R.; Bianchi,
E.; Amisano, P.; Beluffi, G.; Moratti, R.; Liguri, G.: Regional assignment
of the loci for adenylate kinase to 9q32 and for alpha(1)-acid glycoprotein
to 9q31-q32: a locus for Goltz syndrome in region 9q32-qter? Hum.
Genet. 82: 17-19, 1989.
*FIELD* CN
Patricia A. Hartz - updated: 2/26/2009
Carol A. Bocchini - updated: 2/18/2009
Victor A. McKusick - updated: 10/10/2003
Patricia A. Hartz - updated: 6/11/2003
Victor A. McKusick - updated: 6/3/1999
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 03/03/2009
mgross: 2/27/2009
terry: 2/26/2009
terry: 2/18/2009
carol: 2/18/2009
carol: 2/17/2009
terry: 1/7/2009
ckniffin: 3/8/2007
ckniffin: 6/1/2004
mgross: 3/17/2004
tkritzer: 10/21/2003
terry: 10/10/2003
mgross: 6/11/2003
kayiaros: 7/13/1999
carol: 6/15/1999
jlewis: 6/14/1999
jlewis: 6/9/1999
terry: 6/3/1999
terry: 4/29/1999
alopez: 5/8/1998
psherman: 4/15/1998
terry: 8/30/1994
mimadm: 3/11/1994
carol: 5/12/1993
supermim: 3/16/1992
carol: 1/27/1992
carol: 10/3/1991
MIM
612631
*RECORD*
*FIELD* NO
612631
*FIELD* TI
#612631 ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read morehemolytic anemia due to adenylate kinase deficiency is caused by
homozygous or compound heterozygous mutation in the AK1 gene (103000) on
chromosome 9q34.
CLINICAL FEATURES
In 2 offspring of second-cousin Arab parents, Szeinberg et al. (1969)
found marked AK deficiency with intermediate levels in the presumed
heterozygotes. Severe anemia was present in both.
In the study of a black family, Beutler et al. (1982) found that despite
barely detectable levels of adenylate kinase activity, probably
representing guanylate kinase, red cells are able to maintain their
adenine nucleotide levels and to circulate normally. They concluded that
previously reported cases of AK deficiency represent a chance
association of hemolysis with the enzyme deficiency, and not a
cause-and-effect relationship.
In the family reported by Boivin et al. (1971), the proband had
psychomotor retardation and moderate congenital hemolytic anemia with
markedly diminished red cell AK activity. The parents had half-normal AK
activity. Autosomal recessive inheritance was proposed.
Another family, Japanese, was reported by Miwa et al. (1983). The
proband, a 10-year-old girl, had normal physical and mental development,
mild to moderate hemolytic anemia from the neonatal period, and
hepatosplenomegaly. Red cell AK activity was 44% of normal. Puzzlingly,
the proband's mother, younger sister and maternal grandfather showed a
half-normal enzyme activity.
Lachant et al. (1991) reported a fifth family with AK deficiency
associated with hemolytic anemia. In none of the families had a
cause-and-effect relationship to AK deficiency been established. Lachant
et al. (1991) suggested that defects occur in multiple
phosphotransferases in AK-deficient red blood cells and that these other
defects produce deleterious lesions that promote the shortened red cell
survival.
Toren et al. (1994) described a family in which 6 children showed AK
deficiency; in 3 of them, G6PD deficiency was found in combination with
AK deficiency. Although heterozygotes were asymptomatic, homozygotes had
congenital chronic nonspherocytic hemolytic anemia with hemoglobin
levels of 8-9 g/dl. Patients also deficient in G6PD suffered from a more
severe hemolytic anemia with hemoglobin levels around 6 g/dl. The
AK-deficient children were also mentally retarded. Splenectomy performed
in 5 of the 6 children resulted in complete remission of the hemolytic
process.
Bianchi et al. (1999) reported 2 sibs of Italian origin with mild
chronic hemolytic anemia, psychomotor impairment, and undetectable
adenylate kinase activity. They stated that all previously reported
cases except that of Beutler et al. (1983) had chronic nonspherocytic
hemolytic anemia. Psychomotor impairment occurred in only some patients.
MOLECULAR GENETICS
In a patient with hemolytic anemia, Matsuura et al. (1989) demonstrated
a mutation in exon 6 of the AK1 gene, which resulted in an arg128-to-trp
substitution (103000.0001).
In an Italian child with hemolytic anemia and undetectable erythrocyte
adenylate kinase activity, Qualtieri et al. (1997) identified
homozygosity for a tyr164-to-cys substitution (103000.0003) in the AK1
gene.
In 2 sibs of Italian origin with mild chronic hemolytic anemia,
psychomotor impairment, and undetectable adenylate kinase activity,
Bianchi et al. (1999) identified an arg107-to-ter mutation (103000.0002)
in the AK1 gene.
*FIELD* SA
Boivin et al. (1970); Singer and Brock (1971); Szeinberg et al. (1969)
*FIELD* RF
1. Beutler, E.; Carson, D.; Dannawi, H.; Forman, L.; Kuhl, W.; West,
C.; Westwood, B.: Metabolic compensation for profound erythrocyte
adenylate kinase deficiency: a hereditary enzyme defect without hemolytic
anemia. J. Clin. Invest. 72: 648-655, 1983.
2. Beutler, E.; Carson, D. A.; Dannawi, H.; Forman, L.; Kuhl, W.;
West, C.; Westwood, B.: Red cell adenylate kinase deficiency: another
non-disease? (Abstract) Blood 60: 33A only, 1982.
3. Bianchi, P.; Zappa, M.; Bredi, E.; Vercellati, C.; Pelissero, G.;
Barraco, F.; Zanella, A.: A case of complete adenylate kinase deficiency
due to a nonsense mutation in AK-1 gene (arg107-to-stop, CGA-to-TGA)
associated with chronic haemolytic anaemia. Brit. J. Haemat. 105:
75-79, 1999.
4. Boivin, P.; Galand, C.; Hakim, J.; Simony, D.; Seligman, M.: Deficit
congenital en adenylate-kinase erythrocytaire. (Letter) Presse Med. 78:
1443 only, 1970.
5. Boivin, P.; Galand, C.; Hakim, J.; Simony, D.; Seligman, M.: Une
nouvelle erythroenzymopathie: anemie hemolytique congenitale non spherocytaire
et deficit hereditaire en adenylate-kinase erythrocytaire. Presse
Med. 79: 215-218, 1971.
6. Lachant, N. A.; Zerez, C. R.; Barredo, J.; Lee, D. W.; Savely,
S. M.; Tanaka, K. R.: Hereditary erythrocyte adenylate kinase deficiency:
a defect of multiple phosphotransferases? Blood 77: 2774-2784, 1991.
7. Matsuura, S.; Igarashi, M.; Tanizawa, Y.; Yamada, M.; Kishi, F.;
Kajii, T.; Fujii, H.; Miwa, S.; Sakurai, M.; Nakazawa, A.: Human
adenylate kinase deficiency associated with hemolytic anemia: a single
base substitution affecting solubility and catalytic activity of the
cytosolic adenylate kinase. J. Biol. Chem. 264: 10148-10155, 1989.
8. Miwa, S.; Fujii, H.; Tani, K.; Takahashi, K.; Takizawa, T.; Igarashi,
T.: Red cell adenylate kinase deficiency associated with hereditary
nonspherocytic hemolytic anemia: clinical and biochemical studies. Am.
J. Hemat. 14: 325-333, 1983.
9. Qualtieri, A.; Pedace, V.; Bisconte, M. G.; Bria, M.; Gulino, B.;
Andreoli, V.; Brancati, C.: Severe erythrocyte adenylate kinase deficiency
due to homozygous A-to-G substitution at codon 164 of human AK1 gene
associated with chronic haemolytic anaemia. Brit. J. Haemat. 99:
770-776, 1997.
10. Singer, J. D.; Brock, D. J.: Half-normal adenylate kinase activity
in three generations. Ann. Hum. Genet. 35: 109-114, 1971.
11. Szeinberg, A.; Gavendo, S.; Cahane, D.: Erythrocyte adenylate-kinase
deficiency. (Letter) Lancet 293: 315-316, 1969. Note: Originally
Volume I.
12. Szeinberg, A.; Kahana, D.; Gavendo, S.; Zaidman, J.; Ben-Ezzer,
J.: Hereditary deficiency of adenylate kinase in red blood cells. Acta
Haemat. 42: 111-126, 1969.
13. Toren, A.; Brok-Simoni, F.; Ben-Bassat, I.; Holtzman, F.; Mandel,
M.; Neumann, Y.; Ramot, B.; Rechavi, G.; Kende, G.: Congenital haemolytic
anaemia associated with adenylate kinase deficiency. Brit. J. Haemat. 87:
376-380, 1994.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEMATOLOGY:
Hemolytic anemia;
Red cell adenylate kinase deficiency
MOLECULAR BASIS:
Caused by mutation in the adenylate kinase-1 gene (AK1, 103000.0001)
*FIELD* CD
Joanna S. Amberger: 3/8/2012
*FIELD* ED
joanna: 05/10/2012
joanna: 3/8/2012
*FIELD* CD
Carol A. Bocchini: 2/17/2009
*FIELD* ED
carol: 08/05/2013
joanna: 3/8/2012
carol: 11/23/2011
alopez: 8/4/2009
terry: 7/28/2009
carol: 2/18/2009
carol: 2/17/2009
*RECORD*
*FIELD* NO
612631
*FIELD* TI
#612631 ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read morehemolytic anemia due to adenylate kinase deficiency is caused by
homozygous or compound heterozygous mutation in the AK1 gene (103000) on
chromosome 9q34.
CLINICAL FEATURES
In 2 offspring of second-cousin Arab parents, Szeinberg et al. (1969)
found marked AK deficiency with intermediate levels in the presumed
heterozygotes. Severe anemia was present in both.
In the study of a black family, Beutler et al. (1982) found that despite
barely detectable levels of adenylate kinase activity, probably
representing guanylate kinase, red cells are able to maintain their
adenine nucleotide levels and to circulate normally. They concluded that
previously reported cases of AK deficiency represent a chance
association of hemolysis with the enzyme deficiency, and not a
cause-and-effect relationship.
In the family reported by Boivin et al. (1971), the proband had
psychomotor retardation and moderate congenital hemolytic anemia with
markedly diminished red cell AK activity. The parents had half-normal AK
activity. Autosomal recessive inheritance was proposed.
Another family, Japanese, was reported by Miwa et al. (1983). The
proband, a 10-year-old girl, had normal physical and mental development,
mild to moderate hemolytic anemia from the neonatal period, and
hepatosplenomegaly. Red cell AK activity was 44% of normal. Puzzlingly,
the proband's mother, younger sister and maternal grandfather showed a
half-normal enzyme activity.
Lachant et al. (1991) reported a fifth family with AK deficiency
associated with hemolytic anemia. In none of the families had a
cause-and-effect relationship to AK deficiency been established. Lachant
et al. (1991) suggested that defects occur in multiple
phosphotransferases in AK-deficient red blood cells and that these other
defects produce deleterious lesions that promote the shortened red cell
survival.
Toren et al. (1994) described a family in which 6 children showed AK
deficiency; in 3 of them, G6PD deficiency was found in combination with
AK deficiency. Although heterozygotes were asymptomatic, homozygotes had
congenital chronic nonspherocytic hemolytic anemia with hemoglobin
levels of 8-9 g/dl. Patients also deficient in G6PD suffered from a more
severe hemolytic anemia with hemoglobin levels around 6 g/dl. The
AK-deficient children were also mentally retarded. Splenectomy performed
in 5 of the 6 children resulted in complete remission of the hemolytic
process.
Bianchi et al. (1999) reported 2 sibs of Italian origin with mild
chronic hemolytic anemia, psychomotor impairment, and undetectable
adenylate kinase activity. They stated that all previously reported
cases except that of Beutler et al. (1983) had chronic nonspherocytic
hemolytic anemia. Psychomotor impairment occurred in only some patients.
MOLECULAR GENETICS
In a patient with hemolytic anemia, Matsuura et al. (1989) demonstrated
a mutation in exon 6 of the AK1 gene, which resulted in an arg128-to-trp
substitution (103000.0001).
In an Italian child with hemolytic anemia and undetectable erythrocyte
adenylate kinase activity, Qualtieri et al. (1997) identified
homozygosity for a tyr164-to-cys substitution (103000.0003) in the AK1
gene.
In 2 sibs of Italian origin with mild chronic hemolytic anemia,
psychomotor impairment, and undetectable adenylate kinase activity,
Bianchi et al. (1999) identified an arg107-to-ter mutation (103000.0002)
in the AK1 gene.
*FIELD* SA
Boivin et al. (1970); Singer and Brock (1971); Szeinberg et al. (1969)
*FIELD* RF
1. Beutler, E.; Carson, D.; Dannawi, H.; Forman, L.; Kuhl, W.; West,
C.; Westwood, B.: Metabolic compensation for profound erythrocyte
adenylate kinase deficiency: a hereditary enzyme defect without hemolytic
anemia. J. Clin. Invest. 72: 648-655, 1983.
2. Beutler, E.; Carson, D. A.; Dannawi, H.; Forman, L.; Kuhl, W.;
West, C.; Westwood, B.: Red cell adenylate kinase deficiency: another
non-disease? (Abstract) Blood 60: 33A only, 1982.
3. Bianchi, P.; Zappa, M.; Bredi, E.; Vercellati, C.; Pelissero, G.;
Barraco, F.; Zanella, A.: A case of complete adenylate kinase deficiency
due to a nonsense mutation in AK-1 gene (arg107-to-stop, CGA-to-TGA)
associated with chronic haemolytic anaemia. Brit. J. Haemat. 105:
75-79, 1999.
4. Boivin, P.; Galand, C.; Hakim, J.; Simony, D.; Seligman, M.: Deficit
congenital en adenylate-kinase erythrocytaire. (Letter) Presse Med. 78:
1443 only, 1970.
5. Boivin, P.; Galand, C.; Hakim, J.; Simony, D.; Seligman, M.: Une
nouvelle erythroenzymopathie: anemie hemolytique congenitale non spherocytaire
et deficit hereditaire en adenylate-kinase erythrocytaire. Presse
Med. 79: 215-218, 1971.
6. Lachant, N. A.; Zerez, C. R.; Barredo, J.; Lee, D. W.; Savely,
S. M.; Tanaka, K. R.: Hereditary erythrocyte adenylate kinase deficiency:
a defect of multiple phosphotransferases? Blood 77: 2774-2784, 1991.
7. Matsuura, S.; Igarashi, M.; Tanizawa, Y.; Yamada, M.; Kishi, F.;
Kajii, T.; Fujii, H.; Miwa, S.; Sakurai, M.; Nakazawa, A.: Human
adenylate kinase deficiency associated with hemolytic anemia: a single
base substitution affecting solubility and catalytic activity of the
cytosolic adenylate kinase. J. Biol. Chem. 264: 10148-10155, 1989.
8. Miwa, S.; Fujii, H.; Tani, K.; Takahashi, K.; Takizawa, T.; Igarashi,
T.: Red cell adenylate kinase deficiency associated with hereditary
nonspherocytic hemolytic anemia: clinical and biochemical studies. Am.
J. Hemat. 14: 325-333, 1983.
9. Qualtieri, A.; Pedace, V.; Bisconte, M. G.; Bria, M.; Gulino, B.;
Andreoli, V.; Brancati, C.: Severe erythrocyte adenylate kinase deficiency
due to homozygous A-to-G substitution at codon 164 of human AK1 gene
associated with chronic haemolytic anaemia. Brit. J. Haemat. 99:
770-776, 1997.
10. Singer, J. D.; Brock, D. J.: Half-normal adenylate kinase activity
in three generations. Ann. Hum. Genet. 35: 109-114, 1971.
11. Szeinberg, A.; Gavendo, S.; Cahane, D.: Erythrocyte adenylate-kinase
deficiency. (Letter) Lancet 293: 315-316, 1969. Note: Originally
Volume I.
12. Szeinberg, A.; Kahana, D.; Gavendo, S.; Zaidman, J.; Ben-Ezzer,
J.: Hereditary deficiency of adenylate kinase in red blood cells. Acta
Haemat. 42: 111-126, 1969.
13. Toren, A.; Brok-Simoni, F.; Ben-Bassat, I.; Holtzman, F.; Mandel,
M.; Neumann, Y.; Ramot, B.; Rechavi, G.; Kende, G.: Congenital haemolytic
anaemia associated with adenylate kinase deficiency. Brit. J. Haemat. 87:
376-380, 1994.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEMATOLOGY:
Hemolytic anemia;
Red cell adenylate kinase deficiency
MOLECULAR BASIS:
Caused by mutation in the adenylate kinase-1 gene (AK1, 103000.0001)
*FIELD* CD
Joanna S. Amberger: 3/8/2012
*FIELD* ED
joanna: 05/10/2012
joanna: 3/8/2012
*FIELD* CD
Carol A. Bocchini: 2/17/2009
*FIELD* ED
carol: 08/05/2013
joanna: 3/8/2012
carol: 11/23/2011
alopez: 8/4/2009
terry: 7/28/2009
carol: 2/18/2009
carol: 2/17/2009