KPB2_HUMAN
ID KPB2_HUMAN Reviewed; 1235 AA.
AC P46019; A8K1T1; Q6LAJ5; Q7Z6W0; Q96CR3; Q9UDA1;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Phosphorylase b kinase regulatory subunit alpha, liver isoform;
DE Short=Phosphorylase kinase alpha L subunit;
GN Name=PHKA2; Synonyms=PHKLA, PYK;
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 VARIANTS GSD9A PHE-141 DEL AND LEU-1205.
RC TISSUE=Liver;
RX PubMed=7847371;
RA van den Berg I.E.T., van Beurden E.A.C.M., Malingre H.E.M.,
RA Ploos van Amstel H.K., Poll-The B.T., Smeitink J.A.M., Lamers W.H.,
RA Berger R.;
RT "X-linked liver phosphorylase kinase deficiency is associated with
RT mutations in the human liver phosphorylase kinase alpha subunit.";
RL Am. J. Hum. Genet. 56:381-387(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GSD9A VAL-193.
RC TISSUE=Liver;
RX PubMed=7549948;
RA Hirono H., Hayasaka K., Sato W., Takahashi T., Takada G.;
RT "Isolation of cDNA encoding the human liver phosphorylase kinase alpha
RT subunit (PHKA2) and identification of a missense mutation of the PHKA2 gene
RT in a family with liver phosphorylase kinase deficiency.";
RL Biochem. Mol. Biol. Int. 36:505-511(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GSD9A CYS-186; HIS-186;
RP 189-LYS-THR-190 DEL; HIS-295 AND LYS-1125.
RC TISSUE=Liver;
RX PubMed=10330341; DOI=10.1086/302399;
RA Hendrickx J., Lee P., Keating J.P., Carton D., Sardharwalla I.B.,
RA Tuchman M., Baussan C., Willems P.J.;
RT "Complete genomic structure and mutational spectrum of PHKA2 in patients
RT with X-linked liver glycogenosis type I and II.";
RL Am. J. Hum. Genet. 64:1541-1549(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-206, AND VARIANTS GSD9A GLU-189;
RP SER-399; 818-GLN--TYR-825 DEL; 953-ASN--LEU-954 DELINS ILE AND TRP-1207.
RX PubMed=9600238; DOI=10.1007/s004390050715;
RA Burwinkel B., Amat L., Gray R.G., Matsuo N., Muroya K., Narisawa K.,
RA Sokol R.J., Vilaseca M.A., Kilimann M.W.;
RT "Variability of biochemical and clinical phenotype in X-linked liver
RT glycogenosis with mutations in the phosphorylase kinase PHKA2 gene.";
RL Hum. Genet. 102:423-429(1998).
RN [9]
RP NUCLEOTIDE SEQUENCE OF 750-1126.
RC TISSUE=Liver;
RX PubMed=8518797; DOI=10.1093/hmg/2.5.583;
RA Hendrickx J., Coucke P., Bossuyt P., Wauters J., Raeymaekers P.,
RA Marchau F., Smit G.P., Stolte I., Sardharwalla I.B., Berthelot J.;
RT "X-linked liver glycogenosis: localization and isolation of a candidate
RT gene.";
RL Hum. Mol. Genet. 2:583-589(1993).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 977-1080.
RC TISSUE=Liver;
RX PubMed=8226841; DOI=10.1016/s0021-9258(19)49449-0;
RA Wuellrich A., Hamacher C., Schneider A., Kilimann M.W.;
RT "The multiphosphorylation domain of the phosphorylase kinase alpha M and
RT alpha L subunits is a hotspot of differential mRNA processing and of
RT molecular evolution.";
RL J. Biol. Chem. 268:23208-23214(1993).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729; SER-735 AND SER-1015,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1015, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729 AND SER-1015, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729 AND SER-735, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695; SER-729; SER-735 AND
RP SER-1015, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729; SER-983 AND SER-1044,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP VARIANTS GSD9A CYS-186; THR-251 DEL; THR-ARG-1111 INS AND ILE-1114.
RX PubMed=8733133; DOI=10.1093/hmg/5.5.649;
RA Hendrickx J., Dams E., Coucke P., Lee P., Fernandes J., Willems P.J.;
RT "X-linked liver glycogenosis type II (XLG II) is caused by mutations in
RT PHKA2, the gene encoding the liver alpha subunit of phosphorylase kinase.";
RL Hum. Mol. Genet. 5:649-652(1996).
RN [20]
RP VARIANTS GSD9A PRO-132; TYR-132; HIS-186 AND GLY-299.
RX PubMed=8733134; DOI=10.1093/hmg/5.5.653;
RA Burwinkel B., Shin Y.S., Bakker H.D., Deutsch J., Lozano M.J., Maire I.,
RA Kilimann M.W.;
RT "Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis due to
RT phosphorylase kinase deficiency with atypical activity in blood cells
RT (XLG2).";
RL Hum. Mol. Genet. 5:653-658(1996).
RN [21]
RP VARIANTS GSD9A TYR-ASN-THR-ALA-THR-120 INS; GLY-299; LEU-498; ARG-869;
RP TRP-916; ARG-1070 DEL AND ILE-1113.
RX PubMed=17689125; DOI=10.1016/j.ymgme.2007.06.007;
RA Beauchamp N.J., Dalton A., Ramaswami U., Niinikoski H., Mention K.,
RA Kenny P., Kolho K.L., Raiman J., Walter J., Treacy E., Tanner S.,
RA Sharrard M.;
RT "Glycogen storage disease type IX: High variability in clinical
RT phenotype.";
RL Mol. Genet. Metab. 92:88-99(2007).
CC -!- FUNCTION: Phosphorylase b kinase catalyzes the phosphorylation of
CC serine in certain substrates, including troponin I. The alpha chain may
CC bind calmodulin.
CC -!- ACTIVITY REGULATION: By phosphorylation of various serine residues and
CC by calcium.
CC -!- PATHWAY: Glycan biosynthesis; glycogen metabolism.
CC -!- SUBUNIT: Hexadecamer of 4 heterotetramers, each composed of alpha,
CC beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB)
CC are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic
CC subunit, and delta is calmodulin.
CC -!- INTERACTION:
CC P46019; Q93100-4: PHKB; NbExp=3; IntAct=EBI-1642846, EBI-11064505;
CC P46019; P15735: PHKG2; NbExp=7; IntAct=EBI-1642846, EBI-1383819;
CC P46019; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1642846, EBI-5235340;
CC P46019; P06132: UROD; NbExp=3; IntAct=EBI-1642846, EBI-2871776;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver and other non-
CC muscle tissues.
CC -!- PTM: Although the final Cys may be farnesylated, the terminal
CC tripeptide is probably not removed, and the C-terminus is not
CC methylated. {ECO:0000250|UniProtKB:P18688}.
CC -!- DISEASE: Glycogen storage disease 9A (GSD9A) [MIM:306000]: A metabolic
CC disorder resulting in a mild liver glycogenosis with clinical symptoms
CC that include hepatomegaly, growth retardation, muscle weakness,
CC elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate
CC transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting
CC hyperketosis. Two subtypes are known: type 1 or classic type with no
CC phosphorylase kinase activity in liver or erythrocytes, and type 2 or
CC variant type with no phosphorylase kinase activity in liver, but normal
CC activity in erythrocytes. Unlike other glycogenosis diseases, glycogen
CC storage disease type 9A is generally a benign condition. Patients
CC improve with age and are often asymptomatic as adults. Accurate
CC diagnosis is therefore also of prognostic interest.
CC {ECO:0000269|PubMed:10330341, ECO:0000269|PubMed:17689125,
CC ECO:0000269|PubMed:7549948, ECO:0000269|PubMed:7847371,
CC ECO:0000269|PubMed:8733133, ECO:0000269|PubMed:8733134,
CC ECO:0000269|PubMed:9600238}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the phosphorylase b kinase regulatory chain
CC family. {ECO:0000305}.
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DR EMBL; X80497; CAA56662.1; -; mRNA.
DR EMBL; D38616; BAA07606.1; -; mRNA.
DR EMBL; AF044572; AAD32846.1; -; Genomic_DNA.
DR EMBL; AF044540; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044541; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044542; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044543; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044544; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044545; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044546; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044547; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044548; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044549; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044550; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044551; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044552; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044553; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044554; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044555; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044556; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044557; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044558; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044559; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044560; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044561; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044562; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044563; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044564; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044565; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044566; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044567; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044568; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044569; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044570; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044571; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AK289996; BAF82685.1; -; mRNA.
DR EMBL; AL096700; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL732509; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471074; EAW98951.1; -; Genomic_DNA.
DR EMBL; BC014036; AAH14036.1; -; mRNA.
DR EMBL; Y15154; CAA75421.1; -; Genomic_DNA.
DR EMBL; X73875; CAA52084.1; -; mRNA.
DR CCDS; CCDS14190.1; -.
DR RefSeq; NP_000283.1; NM_000292.2.
DR AlphaFoldDB; P46019; -.
DR BioGRID; 111274; 68.
DR IntAct; P46019; 20.
DR MINT; P46019; -.
DR STRING; 9606.ENSP00000369274; -.
DR ChEMBL; CHEMBL2906; -.
DR iPTMnet; P46019; -.
DR PhosphoSitePlus; P46019; -.
DR BioMuta; PHKA2; -.
DR DMDM; 1170685; -.
DR EPD; P46019; -.
DR jPOST; P46019; -.
DR MassIVE; P46019; -.
DR MaxQB; P46019; -.
DR PaxDb; P46019; -.
DR PeptideAtlas; P46019; -.
DR PRIDE; P46019; -.
DR ProteomicsDB; 55707; -.
DR Antibodypedia; 24169; 97 antibodies from 25 providers.
DR DNASU; 5256; -.
DR Ensembl; ENST00000379942.5; ENSP00000369274.4; ENSG00000044446.12.
DR GeneID; 5256; -.
DR KEGG; hsa:5256; -.
DR MANE-Select; ENST00000379942.5; ENSP00000369274.4; NM_000292.3; NP_000283.1.
DR UCSC; uc004cyv.5; human.
DR CTD; 5256; -.
DR DisGeNET; 5256; -.
DR GeneCards; PHKA2; -.
DR GeneReviews; PHKA2; -.
DR HGNC; HGNC:8926; PHKA2.
DR HPA; ENSG00000044446; Low tissue specificity.
DR MalaCards; PHKA2; -.
DR MIM; 300798; gene.
DR MIM; 306000; phenotype.
DR neXtProt; NX_P46019; -.
DR OpenTargets; ENSG00000044446; -.
DR Orphanet; 264580; Glycogen storage disease due to liver phosphorylase kinase deficiency.
DR PharmGKB; PA33267; -.
DR VEuPathDB; HostDB:ENSG00000044446; -.
DR eggNOG; KOG3635; Eukaryota.
DR GeneTree; ENSGT00950000183118; -.
DR HOGENOM; CLU_004177_1_0_1; -.
DR InParanoid; P46019; -.
DR OMA; QFEHIEC; -.
DR OrthoDB; 55049at2759; -.
DR PhylomeDB; P46019; -.
DR TreeFam; TF313970; -.
DR BioCyc; MetaCyc:HS00576-MON; -.
DR BRENDA; 2.7.11.19; 2681.
DR PathwayCommons; P46019; -.
DR Reactome; R-HSA-70221; Glycogen breakdown (glycogenolysis).
DR SignaLink; P46019; -.
DR SIGNOR; P46019; -.
DR UniPathway; UPA00163; -.
DR BioGRID-ORCS; 5256; 7 hits in 706 CRISPR screens.
DR ChiTaRS; PHKA2; human.
DR GeneWiki; PHKA2; -.
DR GenomeRNAi; 5256; -.
DR Pharos; P46019; Tbio.
DR PRO; PR:P46019; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P46019; protein.
DR Bgee; ENSG00000044446; Expressed in right lobe of liver and 182 other tissues.
DR Genevisible; P46019; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005964; C:phosphorylase kinase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0004689; F:phosphorylase kinase activity; TAS:ProtInc.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR008928; 6-hairpin_glycosidase_sf.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR011613; GH15-like.
DR InterPro; IPR045583; KPBA/B_C.
DR InterPro; IPR008734; PHK_A/B_su.
DR PANTHER; PTHR10749; PTHR10749; 1.
DR Pfam; PF00723; Glyco_hydro_15; 1.
DR Pfam; PF19292; KPBB_C; 1.
DR SUPFAM; SSF48208; SSF48208; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; Carbohydrate metabolism; Cell membrane;
KW Disease variant; Glycogen metabolism; Glycogen storage disease;
KW Lipoprotein; Membrane; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..1235
FT /note="Phosphorylase b kinase regulatory subunit alpha,
FT liver isoform"
FT /id="PRO_0000057730"
FT REGION 807..837
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT REGION 972..998
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1028..1060
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1059..1099
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 1028..1055
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 983
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1015
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1044
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT LIPID 1232
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P18688"
FT VARIANT 38
FT /note="E -> Q (in dbSNP:rs17313469)"
FT /id="VAR_024563"
FT VARIANT 120
FT /note="T -> TYNTAT (in GSD9A)"
FT /id="VAR_062393"
FT VARIANT 132
FT /note="H -> P (in GSD9A; type 2; dbSNP:rs137852291)"
FT /evidence="ECO:0000269|PubMed:8733134"
FT /id="VAR_006177"
FT VARIANT 132
FT /note="H -> Y (in GSD9A; type 2; dbSNP:rs137852292)"
FT /evidence="ECO:0000269|PubMed:8733134"
FT /id="VAR_006178"
FT VARIANT 141
FT /note="Missing (in GSD9A; type 1; dbSNP:rs587776732)"
FT /evidence="ECO:0000269|PubMed:7847371"
FT /id="VAR_006179"
FT VARIANT 186
FT /note="R -> C (in GSD9A; type 2; dbSNP:rs137852294)"
FT /evidence="ECO:0000269|PubMed:10330341,
FT ECO:0000269|PubMed:8733133"
FT /id="VAR_006180"
FT VARIANT 186
FT /note="R -> H (in GSD9A; type 2; dbSNP:rs137852290)"
FT /evidence="ECO:0000269|PubMed:10330341,
FT ECO:0000269|PubMed:8733134"
FT /id="VAR_006181"
FT VARIANT 189..190
FT /note="Missing (in GSD9A; type 2)"
FT /evidence="ECO:0000269|PubMed:10330341"
FT /id="VAR_012270"
FT VARIANT 189
FT /note="K -> E (in GSD9A; type 2; dbSNP:rs137852295)"
FT /evidence="ECO:0000269|PubMed:9600238"
FT /id="VAR_012269"
FT VARIANT 193
FT /note="G -> V (in GSD9A; type 2)"
FT /evidence="ECO:0000269|PubMed:7549948"
FT /id="VAR_012271"
FT VARIANT 251
FT /note="Missing (in GSD9A; type 2)"
FT /evidence="ECO:0000269|PubMed:8733133"
FT /id="VAR_006182"
FT VARIANT 295
FT /note="R -> H (in GSD9A; type 1 and type 2;
FT dbSNP:rs797044877)"
FT /evidence="ECO:0000269|PubMed:10330341"
FT /id="VAR_012272"
FT VARIANT 299
FT /note="D -> G (in GSD9A; type 2; dbSNP:rs137852289)"
FT /evidence="ECO:0000269|PubMed:17689125,
FT ECO:0000269|PubMed:8733134"
FT /id="VAR_006183"
FT VARIANT 399
FT /note="P -> S (in GSD9A; type 1)"
FT /evidence="ECO:0000269|PubMed:9600238"
FT /id="VAR_012273"
FT VARIANT 416
FT /note="G -> R (in dbSNP:rs16980929)"
FT /id="VAR_050518"
FT VARIANT 498
FT /note="P -> L (in GSD9A; dbSNP:rs199792389)"
FT /evidence="ECO:0000269|PubMed:17689125"
FT /id="VAR_062394"
FT VARIANT 818..825
FT /note="Missing (in GSD9A; type 1)"
FT /evidence="ECO:0000269|PubMed:9600238"
FT /id="VAR_012274"
FT VARIANT 869
FT /note="P -> R (in GSD9A; dbSNP:rs777137574)"
FT /evidence="ECO:0000269|PubMed:17689125"
FT /id="VAR_062395"
FT VARIANT 916
FT /note="R -> W (in GSD9A; dbSNP:rs1569297427)"
FT /evidence="ECO:0000269|PubMed:17689125"
FT /id="VAR_062396"
FT VARIANT 953..954
FT /note="NL -> I (in GSD9A; type 1)"
FT /id="VAR_012275"
FT VARIANT 1070
FT /note="Missing (in GSD9A; dbSNP:rs1555989523)"
FT /evidence="ECO:0000269|PubMed:17689125"
FT /id="VAR_062397"
FT VARIANT 1111
FT /note="R -> RTR (in GSD9A; type 2)"
FT /id="VAR_006184"
FT VARIANT 1113
FT /note="M -> I (in GSD9A)"
FT /evidence="ECO:0000269|PubMed:17689125"
FT /id="VAR_062398"
FT VARIANT 1114
FT /note="T -> I (in GSD9A; type 2; dbSNP:rs137852293)"
FT /evidence="ECO:0000269|PubMed:8733133"
FT /id="VAR_006185"
FT VARIANT 1125
FT /note="E -> K (in GSD9A; type 1; dbSNP:rs1555988071)"
FT /evidence="ECO:0000269|PubMed:10330341"
FT /id="VAR_012276"
FT VARIANT 1205
FT /note="P -> L (in GSD9A; type 1; dbSNP:rs137852288)"
FT /evidence="ECO:0000269|PubMed:7847371"
FT /id="VAR_006186"
FT VARIANT 1207
FT /note="G -> W (in GSD9A; type 1)"
FT /evidence="ECO:0000269|PubMed:9600238"
FT /id="VAR_012277"
FT CONFLICT 527
FT /note="Q -> E (in Ref. 7; AAH14036)"
FT /evidence="ECO:0000305"
FT CONFLICT 756
FT /note="G -> S (in Ref. 7; AAH14036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1235 AA; 138408 MW; 6CA10CFFA86A582A CRC64;
MRSRSNSGVR LDGYARLVQQ TILCYQNPVT GLLSASHEQK DAWVRDNIYS ILAVWGLGMA
YRKNADRDED KAKAYELEQN VVKLMRGLLQ CMMRQVAKVE KFKHTQSTKD SLHAKYNTAT
CGTVVGDDQW GHLQVDATSL FLLFLAQMTA SGLRIIFTLD EVAFIQNLVF YIEAAYKVAD
YGMWERGDKT NQGIPELNAS SVGMAKAALE AIDELDLFGA HGGRKSVIHV LPDEVEHCQS
ILFSMLPRAS TSKEIDAGLL SIISFPAFAV EDVNLVNVTK NEIISKLQGR YGCCRFLRDG
YKTPREDPNR LHYDPAELKL FENIECEWPV FWTYFIIDGV FSGDAVQVQE YREALEGILI
RGKNGIRLVP ELYAVPPNKV DEEYKNPHTV DRVPMGKVPH LWGQSLYILS SLLAEGFLAA
GEIDPLNRRF STSVKPDVVV QVTVLAENNH IKDLLRKHGV NVQSIADIHP IQVQPGRILS
HIYAKLGRNK NMNLSGRPYR HIGVLGTSKL YVIRNQIFTF TPQFTDQHHF YLALDNEMIV
EMLRIELAYL CTCWRMTGRP TLTFPISRTM LTNDGSDIHS AVLSTIRKLE DGYFGGARVK
LGNLSEFLTT SFYTYLTFLD PDCDEKLFDN ASEGTFSPDS DSDLVGYLED TCNQESQDEL
DHYINHLLQS TSLRSYLPPL CKNTEDRHVF SAIHSTRDIL SVMAKAKGLE VPFVPMTLPT
KVLSAHRKSL NLVDSPQPLL EKVPESDFQW PRDDHGDVDC EKLVEQLKDC SNLQDQADIL
YILYVIKGPS WDTNLSGQHG VTVQNLLGEL YGKAGLNQEW GLIRYISGLL RKKVEVLAEA
CTDLLSHQKQ LTVGLPPEPR EKIISAPLPP EELTKLIYEA SGQDISIAVL TQEIVVYLAM
YVRAQPSLFV EMLRLRIGLI IQVMATELAR SLNCSGEEAS ESLMNLSPFD MKNLLHHILS
GKEFGVERSV RPIHSSTSSP TISIHEVGHT GVTKTERSGI NRLRSEMKQM TRRFSADEQF
FSVGQAASSS AHSSKSARSS TPSSPTGTSS SDSGGHHIGW GERQGQWLRR RRLDGAINRV
PVGFYQRVWK ILQKCHGLSI DGYVLPSSTT REMTPHEIKF AVHVESVLNR VPQPEYRQLL
VEAIMVLTLL SDTEMTSIGG IIHVDQIVQM ASQLFLQDQV SIGAMDTLEK DQATGICHFF
YDSAPSGAYG TMTYLTRAVA SYLQELLPNS GCQMQ
