KPB1_RABIT
ID KPB1_RABIT Reviewed; 1237 AA.
AC P18688;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 25-MAY-2022, entry version 145.
DE RecName: Full=Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform;
DE Short=Phosphorylase kinase alpha M subunit;
GN Name=PHKA1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 1-37; 178-274;
RP 303-334; 380-397; 459-472; 589-598; 627-669; 708-719; 722-733; 772-815;
RP 966-1058; 1113-1127 AND 1168-1237 (ISOFORM 1), AND PHOSPHORYLATION AT
RP SER-972; SER-985; SER-1007; SER-1018; SER-1020; SER-1023 AND SER-1030.
RC TISSUE=Skeletal muscle;
RX PubMed=3362857; DOI=10.1073/pnas.85.9.2929;
RA Zander N.F., Meyer H.E., Hoffmann-Posorske E., Crabb J.W.,
RA Heilmeyer L.M.G. Jr., Kilimann M.W.;
RT "cDNA cloning and complete primary structure of skeletal muscle
RT phosphorylase kinase (alpha subunit).";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2929-2933(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RX PubMed=1874721; DOI=10.1016/s0021-9258(18)98453-x;
RA Harmann B., Zander N.F., Kilimann M.W.;
RT "Isoform diversity of phosphorylase kinase alpha and beta subunits
RT generated by alternative RNA splicing.";
RL J. Biol. Chem. 266:15631-15637(1991).
RN [3]
RP PROTEIN SEQUENCE OF 1016-1027.
RX PubMed=164350; DOI=10.1111/j.1432-1033.1975.tb03909.x;
RA Cohen P., Watson D.C., Dixon G.H.;
RT "The hormonal control of activity of skeletal muscle phosphorylase kinase.
RT Amino-acid sequences at the two sites of action of adenosine-3':5'-
RT monophosphate-dependent protein kinase.";
RL Eur. J. Biochem. 51:79-92(1975).
RN [4]
RP PROTEIN SEQUENCE OF 1221-1237, ISOPRENYLATION AT CYS-1234, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=1409665; DOI=10.1073/pnas.89.20.9554;
RA Heilmeyer L.M. Jr., Serwe M., Weber C., Metzger J., Hoffmann-Posorske E.,
RA Meyer H.E.;
RT "Farnesylcysteine, a constituent of the alpha and beta subunits of rabbit
RT skeletal muscle phosphorylase kinase: localization by conversion to S-
RT ethylcysteine and by tandem mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9554-9558(1992).
RN [5]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
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 [6]
RP PROTEIN SEQUENCE OF 966-996 AND 1000-1040, AND PHOSPHORYLATION AT SER-972;
RP SER-985; SER-1007; SER-1018; SER-1020; SER-1023 AND SER-1030.
RX PubMed=2108025; DOI=10.1111/j.1432-1033.1990.tb15413.x;
RA Meyer H.E., Meyer G.F., Dirks H., Heilmeyer L.M.G. Jr.;
RT "Localization of phosphoserine residues in the alpha subunit of rabbit
RT skeletal muscle phosphorylase kinase.";
RL Eur. J. Biochem. 188:367-376(1990).
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=ABC, Alpha;
CC IsoId=P18688-1; Sequence=Displayed;
CC Name=2; Synonyms=BC;
CC IsoId=P18688-2; Sequence=VSP_004701;
CC Name=3; Synonyms=Alpha';
CC IsoId=P18688-3; Sequence=VSP_004699, VSP_004700;
CC -!- TISSUE SPECIFICITY: Isoform 1 predominates in muscle, heart, brain and
CC testis. Isoforms 1 and 2 are expressed in similar quantities in the
CC other tissues. Isoform 3 is highly expressed in slow muscle and heart.
CC -!- PTM: Phosphorylation of Ser-1018 by PKA stimulates the
CC dephosphorylation of the beta subunit and, thus, reverses the initial
CC stimulation of PHK by the faster beta-subunit phosphorylation by PKA,
CC that occurs in muscle in response to adrenaline.
CC {ECO:0000269|PubMed:2108025, ECO:0000269|PubMed:3362857}.
CC -!- PTM: Cys-1234 is farnesylated, but the C-terminal tripeptide is not
CC removed and the cysteine carboxyl is not methylated.
CC {ECO:0000269|PubMed:1409665}.
CC -!- SIMILARITY: Belongs to the phosphorylase b kinase regulatory chain
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J03247; AAA31446.1; ALT_SEQ; mRNA.
DR EMBL; M64656; AAC23909.1; -; mRNA.
DR PIR; A31334; A31334.
DR RefSeq; NP_001159389.1; NM_001165917.1. [P18688-3]
DR AlphaFoldDB; P18688; -.
DR DIP; DIP-44274N; -.
DR IntAct; P18688; 1.
DR MINT; P18688; -.
DR STRING; 9986.ENSOCUP00000024040; -.
DR BindingDB; P18688; -.
DR iPTMnet; P18688; -.
DR PRIDE; P18688; -.
DR GeneID; 100303771; -.
DR KEGG; ocu:100303771; -.
DR CTD; 5255; -.
DR eggNOG; KOG3635; Eukaryota.
DR InParanoid; P18688; -.
DR BRENDA; 2.7.11.19; 1749.
DR UniPathway; UPA00163; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-UniPathway.
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 Alternative splicing; Calmodulin-binding; Carbohydrate metabolism;
KW Cell membrane; Direct protein sequencing; Glycogen metabolism; Lipoprotein;
KW Membrane; Muscle protein; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..1237
FT /note="Phosphorylase b kinase regulatory subunit alpha,
FT skeletal muscle isoform"
FT /id="PRO_0000057729"
FT REGION 810..840
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT REGION 1021..1069
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1060..1100
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 1039..1062
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1234
FT /note="Not methylated"
FT /evidence="ECO:0000269|PubMed:1409665"
FT MOD_RES 629
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64649"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46020"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46020"
FT MOD_RES 758
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46020"
FT MOD_RES 972
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:2108025,
FT ECO:0000269|PubMed:3362857"
FT MOD_RES 981
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46020"
FT MOD_RES 985
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:2108025,
FT ECO:0000269|PubMed:3362857"
FT MOD_RES 1007
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:2108025,
FT ECO:0000269|PubMed:3362857"
FT MOD_RES 1018
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:164350,
FT ECO:0000269|PubMed:2108025, ECO:0000269|PubMed:3362857"
FT MOD_RES 1020
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2108025,
FT ECO:0000269|PubMed:3362857"
FT MOD_RES 1023
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2108025,
FT ECO:0000269|PubMed:3362857"
FT MOD_RES 1030
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2108025,
FT ECO:0000269|PubMed:3362857"
FT MOD_RES 1127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64649"
FT LIPID 1234
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:1409665"
FT VAR_SEQ 654..712
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1874721"
FT /id="VSP_004699"
FT VAR_SEQ 713
FT /note="N -> D (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1874721"
FT /id="VSP_004700"
FT VAR_SEQ 1012..1024
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004701"
SQ SEQUENCE 1237 AA; 138413 MW; 9B53EBA29D4B33FF CRC64;
MRSRSNSGVR LDSYARLVQQ TILCHQNPVT GLLPASYDQK DAWVRDNVYS ILAVWGLGLA
YRKNADRDED KAKAYELEQS VVKLMRGLLH CMIRQVDKVE SFKYSQSTKD SLHAKYNTKT
CATVVGDDQW GHLQLDATSV YLLFLAQMTA SGLHIIHSLD EVNFIQNLVF YIEAAYKTAD
FGIWERGDKT NQGISELNAS SVGMAKAALE ALDELDLFGV KGGPQSVIHV LADEVQHCQS
ILNSLLPRAS TSKEVDASLL SVISFPAFAV EDSKLVEITK QEIITKLQGR YGCCRFLRDG
YKTPKEDPNR LYYEPAELKL FENIECEWPL FWTYFILDGV FSGNAEQVQE YREALEAVLI
KGKNGVPLLP ELYSVPPDKV DEEYQNPHTV DRVPMGKLPH MWGQSLYILG SLMAEGFLAP
GEIDPLNRRF STVPKPDVVV QVSILAETEE IKAILKDKGI NVETIAEVYP IRVQPARILS
HIYSSLGCNN RMKLSGRPYR HMGVLGTSKL YDIRKTIFTF TPQFIDQQQF YLALDNKMIV
EMLRTDLSYL CSRWRMTGQP TITFPISQTM LDEDGTSLNS SILAALRKMQ DGYFGGARIQ
TGKLSEFLTT SCCTHLSFMD PGPEGKLYSE DYDDNYDELE SGDWMDGYNS TSTARCGDEV
ARYLDHLLAH TAPHPKLAPA SQKGGLNRFR AAVQTTCDLM SLVTKAKELH VQNVHMYLPT
KLFQASRPSL NLLDSSHPSQ EDQVPTVRVE VHLPRDQSGE VDFQALVLQL KETSSLQEQA
DILYMLYTMK GPDWDTELYE EGSATVRELL TELYGKVGKI RHWGLIRYIS GILRKKVEAL
DEACTDLLSH QKHLTVGLPP EPREKTISAP LPYEALTRLI EEACEGDMNI SILTQEIMVY
LAMYMRTQPG LFAEMFRLRI GLIIQVMATE LAHSLRCSAE EATEGLMNLS PSAMKNLLHH
ILSGKEFGVE RSVRPTDSNV SPAISIHEIG AVGATKTERT GIMQLKSEIK QVEFRRLSIS
TESQPNGGHS LGADLMSPSF LSPGTSVTPS SGSFPGHHTS KDSRQGQWQR RRRLDGALNR
VPIGFYQKVW KVLQKCHGLS VEGFVLPSST TREMTPGEIK FSVHVESVLN RVPQPEYRQL
LVEAILVLTM LADIEIHSIG SIIAVEKIVH IANDLFLQEQ KTLGADDIML AKDPASGICT
LLYDSAPSGR FGTMTYLSKA AATYVQEFLP HSICAMQ
