SPKAP_HUMAN
ID SPKAP_HUMAN Reviewed; 1700 AA.
AC Q2M3C7; Q68DA3; Q68DR8; Q9C0I5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=A-kinase anchor protein SPHKAP;
DE AltName: Full=SPHK1-interactor and AKAP domain-containing protein;
DE AltName: Full=Sphingosine kinase type 1-interacting protein;
GN Name=SPHKAP; Synonyms=KIAA1678, SKIP;
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 [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 284-1700 (ISOFORM 1), AND VARIANTS GLU-617 AND
RP GLN-847.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 370-1700 (ISOFORM 2), AND
RP VARIANTS GLU-617 AND GLN-847.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP SPHK1.
RX PubMed=12080051; DOI=10.1074/jbc.m202841200;
RA Lacana E., Maceyka M., Milstien S., Spiegel S.;
RT "Cloning and characterization of a protein kinase A anchoring protein
RT (AKAP)-related protein that interacts with and regulates sphingosine kinase
RT 1 activity.";
RL J. Biol. Chem. 277:32947-32953(2002).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH TYPE I
RP REGULATORY SUBUNIT OF PKA, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20394097; DOI=10.1002/cbic.201000058;
RA Kovanich D., van der Heyden M.A., Aye T.T., van Veen T.A., Heck A.J.,
RA Scholten A.;
RT "Sphingosine kinase interacting protein is an A-kinase anchoring protein
RT specific for type I cAMP-dependent protein kinase.";
RL ChemBioChem 11:963-971(2010).
CC -!- FUNCTION: Anchoring protein that binds preferentially to the type I
CC regulatory subunit of c-AMP-dependent protein kinase (PKA type I) and
CC targets it to distinct subcellular compartments. May act as a
CC converging factor linking cAMP and sphingosine signaling pathways.
CC Plays a regulatory role in the modulation of SPHK1.
CC {ECO:0000269|PubMed:12080051, ECO:0000269|PubMed:20394097}.
CC -!- SUBUNIT: Interacts (via the PKA-RII subunit binding domain) with the RI
CC subunit of PKA. Interacts with SPHK1; the interaction greatly reduces
CC SPHK1 activity. {ECO:0000269|PubMed:12080051,
CC ECO:0000269|PubMed:20394097}.
CC -!- INTERACTION:
CC Q2M3C7; Q9NYA1: SPHK1; NbExp=4; IntAct=EBI-1803914, EBI-985303;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12080051,
CC ECO:0000269|PubMed:20394097}. Note=Colocalizes with SPHK1 in the
CC cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q2M3C7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2M3C7-2; Sequence=VSP_031712;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart. Both isoforms abundantly
CC expressed in ventricle. Also expressed in spleen, ovary and brain.
CC {ECO:0000269|PubMed:12080051, ECO:0000269|PubMed:20394097}.
CC -!- DOMAIN: RII-binding site, predicted to form an amphipathic helix, could
CC participate in protein-protein interactions with a complementary
CC surface on the R-subunit dimer. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the AKAP110 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH18152.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CR749297; CAH18152.1; ALT_INIT; mRNA.
DR EMBL; CR749494; CAH18317.1; -; mRNA.
DR EMBL; BC104954; AAI04955.1; -; mRNA.
DR EMBL; BC104956; AAI04957.1; -; mRNA.
DR EMBL; AB051465; BAB21769.1; -; mRNA.
DR CCDS; CCDS33389.1; -. [Q2M3C7-2]
DR CCDS; CCDS46537.1; -. [Q2M3C7-1]
DR RefSeq; NP_001136116.1; NM_001142644.1. [Q2M3C7-1]
DR RefSeq; NP_085126.2; NM_030623.3. [Q2M3C7-2]
DR AlphaFoldDB; Q2M3C7; -.
DR SMR; Q2M3C7; -.
DR BioGRID; 123222; 6.
DR IntAct; Q2M3C7; 3.
DR STRING; 9606.ENSP00000375909; -.
DR GlyGen; Q2M3C7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q2M3C7; -.
DR PhosphoSitePlus; Q2M3C7; -.
DR BioMuta; SPHKAP; -.
DR DMDM; 121941477; -.
DR MassIVE; Q2M3C7; -.
DR PaxDb; Q2M3C7; -.
DR PeptideAtlas; Q2M3C7; -.
DR PRIDE; Q2M3C7; -.
DR ProteomicsDB; 61371; -. [Q2M3C7-1]
DR ProteomicsDB; 61372; -. [Q2M3C7-2]
DR Antibodypedia; 54535; 46 antibodies from 16 providers.
DR DNASU; 80309; -.
DR Ensembl; ENST00000344657.5; ENSP00000339886.5; ENSG00000153820.13. [Q2M3C7-2]
DR Ensembl; ENST00000392056.8; ENSP00000375909.3; ENSG00000153820.13. [Q2M3C7-1]
DR GeneID; 80309; -.
DR KEGG; hsa:80309; -.
DR MANE-Select; ENST00000392056.8; ENSP00000375909.3; NM_001142644.2; NP_001136116.1.
DR UCSC; uc002vpp.3; human. [Q2M3C7-1]
DR CTD; 80309; -.
DR DisGeNET; 80309; -.
DR GeneCards; SPHKAP; -.
DR HGNC; HGNC:30619; SPHKAP.
DR HPA; ENSG00000153820; Group enriched (brain, heart muscle).
DR MIM; 611646; gene.
DR neXtProt; NX_Q2M3C7; -.
DR OpenTargets; ENSG00000153820; -.
DR PharmGKB; PA162404477; -.
DR VEuPathDB; HostDB:ENSG00000153820; -.
DR eggNOG; ENOG502QQ6Q; Eukaryota.
DR GeneTree; ENSGT00940000153313; -.
DR HOGENOM; CLU_243215_0_0_1; -.
DR InParanoid; Q2M3C7; -.
DR OMA; NKESAGH; -.
DR OrthoDB; 33853at2759; -.
DR PhylomeDB; Q2M3C7; -.
DR TreeFam; TF105426; -.
DR PathwayCommons; Q2M3C7; -.
DR SignaLink; Q2M3C7; -.
DR BioGRID-ORCS; 80309; 8 hits in 1063 CRISPR screens.
DR ChiTaRS; SPHKAP; human.
DR GenomeRNAi; 80309; -.
DR Pharos; Q2M3C7; Tbio.
DR PRO; PR:Q2M3C7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q2M3C7; protein.
DR Bgee; ENSG00000153820; Expressed in left ventricle myocardium and 89 other tissues.
DR Genevisible; Q2M3C7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051018; F:protein kinase A binding; IDA:UniProtKB.
DR InterPro; IPR018292; AKAP_110_C.
DR InterPro; IPR008382; SPHK1-interactor_AKAP_110.
DR PANTHER; PTHR10226; PTHR10226; 1.
DR Pfam; PF05716; AKAP_110; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome.
FT CHAIN 1..1700
FT /note="A-kinase anchor protein SPHKAP"
FT /id="PRO_0000320666"
FT REGION 364..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 742..778
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 793..885
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..946
FT /note="PKA-RII subunit binding domain"
FT /evidence="ECO:0000250"
FT REGION 980..1006
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1374..1414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1481..1535
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1585..1604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..778
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 806..832
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 837..855
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 856..885
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1379..1413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1486..1500
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1509..1535
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1588..1604
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1025
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1085
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1107
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1120
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT MOD_RES 1288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NSW3"
FT VAR_SEQ 1546..1574
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214970,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_031712"
FT VARIANT 425
FT /note="G -> R (in dbSNP:rs4283414)"
FT /id="VAR_039263"
FT VARIANT 617
FT /note="K -> E (in dbSNP:rs3811514)"
FT /evidence="ECO:0000269|PubMed:11214970,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_039264"
FT VARIANT 847
FT /note="H -> Q (in dbSNP:rs3811515)"
FT /evidence="ECO:0000269|PubMed:11214970,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_039265"
FT VARIANT 867
FT /note="Q -> R (in dbSNP:rs3828161)"
FT /id="VAR_039266"
FT VARIANT 1603
FT /note="S -> R (in dbSNP:rs16824283)"
FT /id="VAR_059113"
FT CONFLICT 89
FT /note="D -> G (in Ref. 1; CAH18317)"
FT /evidence="ECO:0000305"
FT CONFLICT 483
FT /note="L -> P (in Ref. 1; CAH18317)"
FT /evidence="ECO:0000305"
FT CONFLICT 719
FT /note="F -> S (in Ref. 1; CAH18152)"
FT /evidence="ECO:0000305"
FT CONFLICT 921
FT /note="P -> L (in Ref. 1; CAH18152)"
FT /evidence="ECO:0000305"
FT CONFLICT 1218
FT /note="D -> I (in Ref. 1; CAH18317)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1700 AA; 186456 MW; 3D49589CAC5A1BDE CRC64;
MDGNSLLSVP SNLESSRMYD VLEPQQGRGC GSSGSGPGNS ITACKKVLRS NSLLESTDYW
LQNQRMPCQI GFVEDKSENC ASVCFVNLDV NKDECSTEHL QQKLVNVSPD LPKLISSMNV
QQPKENEIVV LSGLASGNLQ ADFEVSQCPW LPDICLVQCA RGNRPNSTNC IIFEINKFLI
GLELVQERQL HLETNILKLE DDTNCSLSSI EEDFLTASEH LEEESEVDES RNDYENINVS
ANVLESKQLK GATQVEWNCN KEKWLYALED KYINKYPTPL IKTERSPENL TKNTALQSLD
PSAKPSQWKR EAVGNGRQAT HYYHSEAFKG QMEKSQALYI PKDAYFSMMD KDVPSACAVA
EQRSNLNPGD HEDTRNALPP RQDGEVTTGK YATNLAESVL QDAFIRLSQS QSTLPQESAV
SVSVGSSLLP SCYSTKDTVV SRSWNELPKI VVVQSPDGSD AAPQPGISSW PEMEVSVETS
SILSGENSSR QPQSALEVAL ACAATVIGTI SSPQATERLK MEQVVSNFPP GSSGALQTQA
PQGLKEPSIN EYSFPSALCG MTQVASAVAV CGLGEREEVT CSVAPSGSLP PAAEASEAMP
PLCGLASMEL GKEAIAKGLL KEAALVLTRP NTYSSIGDFL DSMNRRIMET ASKSQTLCSE
NVVRNELAHT LSNVILRHSI DEVHHKNMII DPNDNRHSSE ILDTLMESTN QLLLDVICFT
FKKMSHIVRL GECPAVLSKE TIRRRETEPS CQPSDPGASQ AWTKATESSS SSPLSNSHNT
SLVINNLVDG MYSKQDKGGV RPGLFKNPTL QSQLSRSHRV PDSSTATTSS KEIYLKGIAG
EDTKSPHHSE NECRASSEGQ RSPTVSQSRS GSQEAEESIH PNTQEKYNCA TSRINEVQVN
LSLLGDDLLL PAQSTLQTKH PDIYCITDFA EELADTVVSM ATEIAAICLD NSSGKQPWFC
AWKRGSEFLM TPNVPCRSLK RKKESQGSGT AVRKHKPPRL SEIKRKTDEH PELKEKLMNR
VVDESMNLED VPDSVNLFAN EVAAKIMNLT EFSMVDGMWQ AQGYPRNRLL SGDRWSRLKA
SSCESIPEED SEARAYVNSL GLMSTLSQPV SRASSVSKQS SCESITDEFS RFMVNQMENE
GRGFELLLDY YAGKNASSIL NSAMQQACRK SDHLSVRPSC PSKQSSTESI TEEFYRYMLR
DIERDSRESA SSRRSSQDWT AGLLSPSLRS PVCHRQSSMP DSRSPCSRLT VNVPIKANSL
DGFAQNCPQD FLSVQPVSSA SSSGLCKSDS CLYRRGGTDH ITNMLIHETW ASSIEALMRK
NKIIVDDAEE ADTEPVSGGS PSQAEKCANR LAASRMCSGP TLLVQESLDC PRKDSVTECK
QPPVSSLSKT ASLTNHSPLD SKKETSSCQD PVPINHKRRS LCSREVPLIQ IETDQREACA
GEPEPFLSKS SLLEEAEGHS NDKNIPDVVR GGDTAVSACQ IHSDSLDTRD VPEAEASTEA
RAPDEAPNPP SSSEESTGSW TQLANEEDNP DDTSSFLQLS ERSMSNGNSS ATSSLGIMDL
DIYQESMPSS PMINELVEEK KILKGQSEST EAPASGPPTG TASPQRSLLV INFDLEPECP
DAELRATLQW IAASELGIPT IYFKKSQENR IEKFLDVVQL VHRKSWKVGD IFHAVVQYCK
MHEEQKDGRL SLFDWLLELG
