SPDYA_HUMAN
ID SPDYA_HUMAN Reviewed; 313 AA.
AC Q5MJ70; Q53R05; Q5MJ69;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Speedy protein A;
DE AltName: Full=Rapid inducer of G2/M progression in oocytes A;
DE Short=RINGO A;
DE Short=hSpy/Ringo A;
DE AltName: Full=Speedy-1;
DE Short=Spy1;
GN Name=SPDYA {ECO:0000312|HGNC:HGNC:30613};
GN Synonyms=SPDY1 {ECO:0000312|HGNC:HGNC:30613},
GN SPY1 {ECO:0000312|EMBL:AAY24014.1};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDK2,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Testis {ECO:0000269|PubMed:11980914};
RX PubMed=11980914; DOI=10.1083/jcb.200109045;
RA Porter L.A., Dellinger R.W., Tynan J.A., Barnes E.A., Kong M.,
RA Lenormand J.-L., Donoghue D.J.;
RT "Human Speedy: a novel cell cycle regulator that enhances proliferation
RT through activation of Cdk2.";
RL J. Cell Biol. 157:357-366(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAW30395.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Testis {ECO:0000312|EMBL:AAW30394.1};
RX PubMed=15611625; DOI=10.4161/cc.4.1.1347;
RA Cheng A., Xiong W., Ferrell J.E. Jr., Solomon M.J.;
RT "Identification and comparative analysis of multiple mammalian Speedy/Ringo
RT proteins.";
RL Cell Cycle 4:155-165(2005).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAY24014.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH93005.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis {ECO:0000312|EMBL:AAH93005.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH CDK2.
RX PubMed=12839962;
RA Barnes E.A., Porter L.A., Lenormand J.-L., Dellinger R.W., Donoghue D.J.;
RT "Human Spy1 promotes survival of mammalian cells following DNA damage.";
RL Cancer Res. 63:3701-3707(2003).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CDKN1B, IDENTIFICATION IN A COMPLEX WITH CDKN1B
RP AND CDK2, AND SUBCELLULAR LOCATION.
RX PubMed=12972555; DOI=10.1091/mbc.e02-12-0820;
RA Porter L.A., Kong-Beltran M., Donoghue D.J.;
RT "Spy1 interacts with p27Kip1 to allow G1/S progression.";
RL Mol. Biol. Cell 14:3664-3674(2003).
RN [7] {ECO:0007744|PDB:5UQ1, ECO:0007744|PDB:5UQ2, ECO:0007744|PDB:5UQ3}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 61-213 IN COMPLEXES WITH CDK2 AND
RP CDKN1B, SUBUNIT, FUNCTION, INTERACTION WITH CDK2, REGION, AND MUTAGENESIS
RP OF ASP-97 AND GLU-135.
RX PubMed=28666995; DOI=10.15252/embj.201796905;
RA McGrath D.A., Fifield B.A., Marceau A.H., Tripathi S., Porter L.A.,
RA Rubin S.M.;
RT "Structural basis of divergent cyclin-dependent kinase activation by
RT Spy1/RINGO proteins.";
RL EMBO J. 36:2251-2262(2017).
CC -!- FUNCTION: Regulates the G1/S phase transition of the cell cycle by
CC binding and activating CDK1 and CDK2 (PubMed:12972555). Contributes to
CC CDK2 activation without promoting CDK2 phosphorylation, by inducing a
CC conformation change of the CDK2 T-loop that obstructs the substrate-
CC binding cleft prior to kinase activation (PubMed:28666995). Mediates
CC cell survival during the DNA damage process through activation of CDK2
CC (PubMed:12839962). {ECO:0000269|PubMed:11980914,
CC ECO:0000269|PubMed:12839962, ECO:0000269|PubMed:12972555,
CC ECO:0000269|PubMed:28666995}.
CC -!- SUBUNIT: Interacts with CDK1 (By similarity). Interacts with CDK2
CC (PubMed:11980914, PubMed:12839962, PubMed:12972555, PubMed:28666995).
CC May interact with CDKN1B/KIP1 (PubMed:12972555). Identified in a
CC complex with CDK2 and CDKN1B/KIP1, where it interacts primarily with
CC CDK2 (PubMed:12972555, PubMed:28666995). {ECO:0000250|UniProtKB:Q5IBH7,
CC ECO:0000269|PubMed:11980914, ECO:0000269|PubMed:12839962,
CC ECO:0000269|PubMed:12972555, ECO:0000269|PubMed:28666995}.
CC -!- INTERACTION:
CC Q5MJ70; P29972: AQP1; NbExp=3; IntAct=EBI-7125479, EBI-745213;
CC Q5MJ70; Q00535: CDK5; NbExp=3; IntAct=EBI-7125479, EBI-1041567;
CC Q5MJ70; P46527: CDKN1B; NbExp=3; IntAct=EBI-7125479, EBI-519280;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11980914,
CC ECO:0000269|PubMed:12972555}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2 {ECO:0000269|PubMed:15611625, ECO:0000269|PubMed:15815621};
CC Synonyms=A2 {ECO:0000269|PubMed:15611625};
CC IsoId=Q5MJ70-2; Sequence=Displayed;
CC Name=1 {ECO:0000269|PubMed:15611625}; Synonyms=A1
CC {ECO:0000269|PubMed:15611625};
CC IsoId=Q5MJ70-1; Sequence=VSP_052027, VSP_052028;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Expressed at a low
CC level in wide range of tissues including bone marrow, brain, heart,
CC kidney, colon, liver, placenta, spleen, skeletal muscle, salivary
CC gland, thyroid gland, thymus, trachea and uterus. Expressed at a
CC slightly higher level in adrenal gland, cerebellum, small intestine,
CC lung, prostate and trachea. Expression is cell cycle-dependent, being
CC restricted to cells in G1/S phase. {ECO:0000269|PubMed:11980914,
CC ECO:0000269|PubMed:15611625}.
CC -!- DOMAIN: The C-terminus is required for CDK2-activation, but not CDK2-
CC binding. {ECO:0000250|UniProtKB:Q5IBH7}.
CC -!- SIMILARITY: Belongs to the Speedy/Ringo family. {ECO:0000305}.
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DR EMBL; AY820303; AAW30394.1; -; mRNA.
DR EMBL; AY820304; AAW30395.1; -; mRNA.
DR EMBL; AC097720; AAY24014.1; -; Genomic_DNA.
DR EMBL; BC093005; AAH93005.1; -; mRNA.
DR CCDS; CCDS1767.2; -. [Q5MJ70-2]
DR RefSeq; NP_001008779.1; NM_001008779.1. [Q5MJ70-1]
DR RefSeq; NP_001136106.1; NM_001142634.1. [Q5MJ70-2]
DR RefSeq; NP_877433.2; NM_182756.3. [Q5MJ70-2]
DR PDB; 5UQ1; X-ray; 3.20 A; B/D=61-213.
DR PDB; 5UQ2; X-ray; 2.70 A; B=61-213.
DR PDB; 5UQ3; X-ray; 3.60 A; B=61-213.
DR PDB; 7E34; X-ray; 3.19 A; B=61-213.
DR PDBsum; 5UQ1; -.
DR PDBsum; 5UQ2; -.
DR PDBsum; 5UQ3; -.
DR PDBsum; 7E34; -.
DR AlphaFoldDB; Q5MJ70; -.
DR SMR; Q5MJ70; -.
DR BioGRID; 128828; 10.
DR IntAct; Q5MJ70; 6.
DR MINT; Q5MJ70; -.
DR STRING; 9606.ENSP00000335628; -.
DR iPTMnet; Q5MJ70; -.
DR PhosphoSitePlus; Q5MJ70; -.
DR BioMuta; SPDYA; -.
DR DMDM; 94730574; -.
DR MassIVE; Q5MJ70; -.
DR PaxDb; Q5MJ70; -.
DR PeptideAtlas; Q5MJ70; -.
DR PRIDE; Q5MJ70; -.
DR ProteomicsDB; 63585; -. [Q5MJ70-2]
DR ProteomicsDB; 63586; -. [Q5MJ70-1]
DR Antibodypedia; 28865; 220 antibodies from 26 providers.
DR DNASU; 245711; -.
DR Ensembl; ENST00000334056.10; ENSP00000335628.5; ENSG00000163806.16. [Q5MJ70-2]
DR Ensembl; ENST00000379579.8; ENSP00000368898.4; ENSG00000163806.16. [Q5MJ70-2]
DR GeneID; 245711; -.
DR KEGG; hsa:245711; -.
DR MANE-Select; ENST00000334056.10; ENSP00000335628.5; NM_182756.4; NP_877433.2.
DR UCSC; uc002rmj.4; human. [Q5MJ70-2]
DR CTD; 245711; -.
DR DisGeNET; 245711; -.
DR GeneCards; SPDYA; -.
DR HGNC; HGNC:30613; SPDYA.
DR HPA; ENSG00000163806; Tissue enriched (testis).
DR MIM; 614029; gene.
DR neXtProt; NX_Q5MJ70; -.
DR OpenTargets; ENSG00000163806; -.
DR PharmGKB; PA134954857; -.
DR VEuPathDB; HostDB:ENSG00000163806; -.
DR eggNOG; KOG3938; Eukaryota.
DR GeneTree; ENSGT00940000154524; -.
DR HOGENOM; CLU_070353_1_2_1; -.
DR InParanoid; Q5MJ70; -.
DR OMA; VCQTPPT; -.
DR OrthoDB; 1480540at2759; -.
DR PhylomeDB; Q5MJ70; -.
DR TreeFam; TF329827; -.
DR PathwayCommons; Q5MJ70; -.
DR SignaLink; Q5MJ70; -.
DR SIGNOR; Q5MJ70; -.
DR BioGRID-ORCS; 245711; 8 hits in 1070 CRISPR screens.
DR ChiTaRS; SPDYA; human.
DR GeneWiki; SPDYA; -.
DR GenomeRNAi; 245711; -.
DR Pharos; Q5MJ70; Tbio.
DR PRO; PR:Q5MJ70; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q5MJ70; protein.
DR Bgee; ENSG00000163806; Expressed in left testis and 97 other tissues.
DR ExpressionAtlas; Q5MJ70; baseline and differential.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR InterPro; IPR020984; Speedy.
DR Pfam; PF11357; Spy1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Developmental protein;
KW DNA damage; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..313
FT /note="Speedy protein A"
FT /id="PRO_0000234112"
FT REGION 68..200
FT /note="Speedy/Ringo box; Required for CDK-binding"
FT /evidence="ECO:0000269|PubMed:28666995"
FT REGION 278..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..313
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5IBH7"
FT MOD_RES 224
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5IBH7"
FT VAR_SEQ 284..286
FT /note="VVN -> GMI (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:11980914,
FT ECO:0000303|PubMed:15611625"
FT /id="VSP_052027"
FT VAR_SEQ 287..313
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:11980914,
FT ECO:0000303|PubMed:15611625"
FT /id="VSP_052028"
FT MUTAGEN 97
FT /note="D->N: Loss of CDK2 activation; when associated with
FT Q-135."
FT /evidence="ECO:0000269|PubMed:28666995"
FT MUTAGEN 135
FT /note="E->Q: Loss of CDK2 activation; when associated with
FT N-97."
FT /evidence="ECO:0000269|PubMed:28666995"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:7E34"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 76..79
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 81..89
FT /evidence="ECO:0007829|PDB:5UQ2"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 98..110
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 120..134
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 144..149
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:7E34"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 157..170
FT /evidence="ECO:0007829|PDB:5UQ2"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:5UQ2"
FT HELIX 179..185
FT /evidence="ECO:0007829|PDB:5UQ2"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:5UQ1"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:5UQ2"
SQ SEQUENCE 313 AA; 36463 MW; F511EECB26245EEC CRC64;
MRHNQMCCET PPTVTVYVKS GSNRSHQPKK PITLKRPICK DNWQAFEKNT HNNNKSKRPK
GPCLVIQRQD MTAFFKLFDD DLIQDFLWMD CCCKIADKYL LAMTFVYFKR AKFTISEHTR
INFFIALYLA NTVEEDEEET KYEIFPWALG KNWRKLFPNF LKLRDQLWDR IDYRAIVSRR
CCEEVMAIAP THYIWQRERS VHHSGAVRNY NRDEVQLPRG PSATPVDCSL CGKKRRYVRL
GLSSSSSLSS HTAGVTEKHS QDSYNSLSMD IIGDPSQAYT GSEVVNDHQS NKGKKTNFLK
KDKSMEWFTG SEE