RGPA1_HUMAN
ID RGPA1_HUMAN Reviewed; 2036 AA.
AC Q6GYQ0; A6NMA4; B9EK38; C5NU19; O94960; Q6GYP9; Q6ZT23; Q86YF3; Q86YF5;
AC Q8ND69;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Ral GTPase-activating protein subunit alpha-1;
DE AltName: Full=GAP-related-interacting partner to E12;
DE Short=GRIPE;
DE AltName: Full=GTPase-activating Rap/Ran-GAP domain-like 1;
DE AltName: Full=Tuberin-like protein 1;
DE AltName: Full=p240;
GN Name=RALGAPA1; Synonyms=GARNL1, KIAA0884, TULIP1;
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] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=15498464; DOI=10.1016/j.ygeno.2004.04.013;
RA Schwarzbraun T., Vincent J.B., Schumacher A., Geschwind D.H., Oliveira J.,
RA Windpassinger C., Ofner L., Ledinegg M.K., Kroisel P.M., Wagner K.,
RA Petek E.;
RT "Cloning, genomic structure and expression profile of TULIP1 (GARNL1), a
RT brain-expressed candidate gene for 14q13-linked neurological phenotypes and
RT its murine homolog.";
RL Genomics 84:577-586(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), VARIANT ALA-931, AND MUTAGENESIS OF
RP ASN-1903.
RX PubMed=19520869; DOI=10.1074/jbc.m109.012112;
RA Shirakawa R., Fukai S., Kawato M., Higashi T., Kondo H., Ikeda T.,
RA Nakayama E., Okawa K., Nureki O., Kimura T., Kita T., Horiuchi H.;
RT "Tuberous sclerosis tumor suppressor complex-like complexes act as GTPase-
RT activating proteins for Ral GTPases.";
RL J. Biol. Chem. 284:21580-21588(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1147-2036 (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 1719-2036 (ISOFORM 5).
RC TISSUE=Brain, and Skin;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1167-2036 (ISOFORM 4).
RC TISSUE=Lymph node;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1361-2036 (ISOFORM 2).
RC TISSUE=Brain;
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-778, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-773, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-797, AND IDENTIFICATION BY
RP 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-754 AND SER-773, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-754; SER-860; SER-861 AND
RP SER-864, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-711; SER-721; THR-754;
RP SER-773; SER-797; SER-860 AND SER-861, AND IDENTIFICATION BY MASS
RP 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-986; SER-990 AND SER-994, AND
RP 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 [17]
RP INVOLVEMENT IN NEDHRIT, VARIANTS NEDHRIT 204-GLU--HIS-2036 DEL;
RP 376-ARG--HIS-2036 DEL; SER-1076 AND 1911-SER--HIS-2036 DEL, AND
RP CHARACTERIZATION OF VARIANT NEDHRIT SER-1076.
RX PubMed=32004447; DOI=10.1016/j.ajhg.2020.01.002;
RA Wagner M., Skorobogatko Y., Pode-Shakked B., Powell C.M., Alhaddad B.,
RA Seibt A., Barel O., Heimer G., Hoffmann C., Demmer L.A., Perilla-Young Y.,
RA Remke M., Wieczorek D., Navaratnarajah T., Lichtner P., Klee D.,
RA Shamseldin H.E., Al Mutairi F., Mayatepek E., Strom T., Meitinger T.,
RA Alkuraya F.S., Anikster Y., Saltiel A.R., Distelmaier F.;
RT "Bi-allelic variants in RALGAPA1 cause profound neurodevelopmental
RT disability, muscular hypotonia, infantile spasms, and feeding
RT abnormalities.";
RL Am. J. Hum. Genet. 106:246-255(2020).
CC -!- FUNCTION: Catalytic subunit of the heterodimeric RalGAP1 complex which
CC acts as a GTPase activator for the Ras-like small GTPases RALA and
CC RALB. {ECO:0000250}.
CC -!- SUBUNIT: Component of the heterodimeric RalGAP1 complex with RALGAPB.
CC Heterodimerization is required for activity. Interacts with the HLH
CC region of TCF3/isoform E12 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Translocated to the nucleus, when associated with TCF3/E12.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q6GYQ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6GYQ0-2; Sequence=VSP_011328;
CC Name=3;
CC IsoId=Q6GYQ0-3; Sequence=VSP_011324, VSP_011325, VSP_011326;
CC Name=4;
CC IsoId=Q6GYQ0-4; Sequence=VSP_011327;
CC Name=5;
CC IsoId=Q6GYQ0-5; Sequence=VSP_011329;
CC Name=6;
CC IsoId=Q6GYQ0-6; Sequence=VSP_011324;
CC Name=7;
CC IsoId=Q6GYQ0-7; Sequence=VSP_054485;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:15498464}.
CC -!- DISEASE: Neurodevelopmental disorder with hypotonia, neonatal
CC respiratory insufficiency, and thermodysregulation (NEDHRIT)
CC [MIM:618797]: An autosomal recessive disorder characterized by profound
CC neurodevelopmental disability, muscular hypotonia, feeding
CC abnormalities, recurrent fever episodes, infantile spasms, and moderate
CC dysmorphic facial features. Brain imaging shows thin corpus or
CC dysplastic corpus callosum, and additional unspecific abnormalities
CC including gray matter heterotopias, ectopic posterior pituitary, signal
CC abnormalities in basal ganglia, and stratum subependymale.
CC {ECO:0000269|PubMed:32004447}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC86772.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY596970; AAT49271.1; -; mRNA.
DR EMBL; AY596971; AAT49272.1; -; mRNA.
DR EMBL; AB511280; BAH83561.1; -; mRNA.
DR EMBL; AB020691; BAA74907.1; -; mRNA.
DR EMBL; AL137818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042013; AAH42013.1; -; mRNA.
DR EMBL; BC042045; AAH42045.1; -; mRNA.
DR EMBL; BC150596; AAI50597.1; -; mRNA.
DR EMBL; AL834362; CAD39026.1; -; mRNA.
DR EMBL; AK126975; BAC86772.1; ALT_INIT; mRNA.
DR CCDS; CCDS32064.1; -. [Q6GYQ0-2]
DR CCDS; CCDS32065.1; -. [Q6GYQ0-1]
DR CCDS; CCDS61439.1; -. [Q6GYQ0-7]
DR CCDS; CCDS61440.1; -. [Q6GYQ0-6]
DR RefSeq; NP_001269972.1; NM_001283043.2. [Q6GYQ0-7]
DR RefSeq; NP_001269973.1; NM_001283044.2. [Q6GYQ0-6]
DR RefSeq; NP_001317004.1; NM_001330075.2.
DR RefSeq; NP_001333172.1; NM_001346243.1. [Q6GYQ0-1]
DR RefSeq; NP_001333174.1; NM_001346245.1. [Q6GYQ0-6]
DR RefSeq; NP_001333175.1; NM_001346246.1.
DR RefSeq; NP_001333176.1; NM_001346247.1.
DR RefSeq; NP_001333177.1; NM_001346248.1.
DR RefSeq; NP_001333178.1; NM_001346249.1.
DR RefSeq; NP_055805.1; NM_014990.2. [Q6GYQ0-1]
DR RefSeq; NP_919277.2; NM_194301.3. [Q6GYQ0-2]
DR AlphaFoldDB; Q6GYQ0; -.
DR BioGRID; 128998; 63.
DR IntAct; Q6GYQ0; 19.
DR MINT; Q6GYQ0; -.
DR STRING; 9606.ENSP00000302647; -.
DR GlyGen; Q6GYQ0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6GYQ0; -.
DR PhosphoSitePlus; Q6GYQ0; -.
DR BioMuta; RALGAPA1; -.
DR DMDM; 51315850; -.
DR EPD; Q6GYQ0; -.
DR jPOST; Q6GYQ0; -.
DR MassIVE; Q6GYQ0; -.
DR MaxQB; Q6GYQ0; -.
DR PaxDb; Q6GYQ0; -.
DR PeptideAtlas; Q6GYQ0; -.
DR PRIDE; Q6GYQ0; -.
DR ProteomicsDB; 66328; -. [Q6GYQ0-1]
DR ProteomicsDB; 66329; -. [Q6GYQ0-2]
DR ProteomicsDB; 66330; -. [Q6GYQ0-3]
DR ProteomicsDB; 66331; -. [Q6GYQ0-4]
DR ProteomicsDB; 66332; -. [Q6GYQ0-5]
DR ProteomicsDB; 66333; -. [Q6GYQ0-6]
DR ProteomicsDB; 7535; -.
DR Antibodypedia; 79; 85 antibodies from 20 providers.
DR DNASU; 253959; -.
DR Ensembl; ENST00000307138.10; ENSP00000302647.6; ENSG00000174373.17. [Q6GYQ0-2]
DR Ensembl; ENST00000382366.7; ENSP00000371803.3; ENSG00000174373.17. [Q6GYQ0-7]
DR Ensembl; ENST00000389698.7; ENSP00000374348.3; ENSG00000174373.17. [Q6GYQ0-1]
DR Ensembl; ENST00000553892.2; ENSP00000451877.1; ENSG00000174373.17. [Q6GYQ0-6]
DR GeneID; 253959; -.
DR KEGG; hsa:253959; -.
DR UCSC; uc001wti.3; human. [Q6GYQ0-1]
DR CTD; 253959; -.
DR DisGeNET; 253959; -.
DR GeneCards; RALGAPA1; -.
DR HGNC; HGNC:17770; RALGAPA1.
DR HPA; ENSG00000174373; Low tissue specificity.
DR MalaCards; RALGAPA1; -.
DR MIM; 608884; gene.
DR MIM; 618797; phenotype.
DR neXtProt; NX_Q6GYQ0; -.
DR OpenTargets; ENSG00000174373; -.
DR PharmGKB; PA165479278; -.
DR VEuPathDB; HostDB:ENSG00000174373; -.
DR eggNOG; KOG3686; Eukaryota.
DR GeneTree; ENSGT00950000183139; -.
DR HOGENOM; CLU_001676_0_0_1; -.
DR InParanoid; Q6GYQ0; -.
DR OMA; FLEVIYH; -.
DR OrthoDB; 157372at2759; -.
DR PhylomeDB; Q6GYQ0; -.
DR TreeFam; TF324484; -.
DR PathwayCommons; Q6GYQ0; -.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR SignaLink; Q6GYQ0; -.
DR BioGRID-ORCS; 253959; 36 hits in 1097 CRISPR screens.
DR ChiTaRS; RALGAPA1; human.
DR GeneWiki; GARNL1; -.
DR GenomeRNAi; 253959; -.
DR Pharos; Q6GYQ0; Tbio.
DR PRO; PR:Q6GYQ0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q6GYQ0; protein.
DR Bgee; ENSG00000174373; Expressed in endothelial cell and 197 other tissues.
DR ExpressionAtlas; Q6GYQ0; baseline and differential.
DR Genevisible; Q6GYQ0; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR Gene3D; 3.40.50.11210; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035974; Rap/Ran-GAP_sf.
DR InterPro; IPR000331; Rap/Ran_GAP_dom.
DR InterPro; IPR027107; Tuberin/Ral-act_asu.
DR PANTHER; PTHR10063; PTHR10063; 1.
DR Pfam; PF02145; Rap_GAP; 1.
DR SUPFAM; SSF111347; SSF111347; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50085; RAPGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Disease variant;
KW GTPase activation; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..2036
FT /note="Ral GTPase-activating protein subunit alpha-1"
FT /id="PRO_0000056753"
FT DOMAIN 1796..2004
FT /note="Rap-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00165"
FT REGION 343..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 715..753
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 982..1009
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1327..2035
FT /note="Minimal domain that binds to TCF3/E12"
FT /evidence="ECO:0000250"
FT COILED 1716..1744
FT /evidence="ECO:0000255"
FT COMPBIAS 348..363
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 364..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 715..747
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 894..910
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 721
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 754
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 778
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 797
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 860
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 986
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 990
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 994
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1000
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O55007"
FT MOD_RES 1002
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6GYP7"
FT MOD_RES 1004
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O55007"
FT MOD_RES 1478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O55007"
FT VAR_SEQ 755
FT /note="V -> VAMRSRSIGECALPSAYIRSAKSAPVLIHTSKPFLPDIVLTPLSDEL
FT S (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:19520869"
FT /id="VSP_011324"
FT VAR_SEQ 812..825
FT /note="VNKEDMSQKLPPLN -> EAEQNATRGSTEGSVQSCNGLFWKESC (in
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054485"
FT VAR_SEQ 1036..1057
FT /note="EISEFPSECCSVMAGGTLTGWH -> GNISKLDIYLFSFRASVSGDHK (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:10048485"
FT /id="VSP_011325"
FT VAR_SEQ 1058..2036
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10048485"
FT /id="VSP_011326"
FT VAR_SEQ 1898..2036
FT /note="LRHLGNDEVHIVWSEHTRDYRRGIIPTEFGDVLIVIYPMKNHMFSIQIMKKP
FT EVPFFGPLFDGAIVNGKVLPIMVRATAINASRALKSLIPLYQNFYEERARYLQTIVQHH
FT LEPTTFEDFAAQVFSPAPYHHLPSDADH -> MESHCVAQAGVQWHDLRSLQLLPPRFK
FT ESSLLSLLSSWDYRCMPPHLSNFCIFSRDGVSPCWPG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_011327"
FT VAR_SEQ 2035..2036
FT /note="DH -> GSYPEILPSETPTATQVDGADLASPMSPRTSKSRMSMKLRRSSGSA
FT NKS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15498464"
FT /id="VSP_011328"
FT VAR_SEQ 2035..2036
FT /note="DH -> VERNAVIVLFLPKPPLENIGHLKAPTQRFYPVKLPQQRR (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011329"
FT VARIANT 204..2036
FT /note="Missing (in NEDHRIT)"
FT /evidence="ECO:0000269|PubMed:32004447"
FT /id="VAR_083728"
FT VARIANT 376..2036
FT /note="Missing (in NEDHRIT)"
FT /evidence="ECO:0000269|PubMed:32004447"
FT /id="VAR_083729"
FT VARIANT 931
FT /note="T -> A (in dbSNP:rs2274068)"
FT /evidence="ECO:0000269|PubMed:19520869"
FT /id="VAR_019804"
FT VARIANT 1076
FT /note="N -> S (in NEDHRIT; undetectable protein expression;
FT dbSNP:rs1595085511)"
FT /evidence="ECO:0000269|PubMed:32004447"
FT /id="VAR_083730"
FT VARIANT 1911..2036
FT /note="Missing (in NEDHRIT)"
FT /evidence="ECO:0000269|PubMed:32004447"
FT /id="VAR_083731"
FT MUTAGEN 1903
FT /note="N->K: Has no effect on interaction with RALGAPB but
FT causes loss of activity."
FT /evidence="ECO:0000269|PubMed:19520869"
FT CONFLICT 779
FT /note="G -> A (in Ref. 3; BAA74907)"
FT /evidence="ECO:0000305"
FT CONFLICT 1270
FT /note="K -> N (in Ref. 6; CAD39026)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2036 AA; 229832 MW; 7ADF5487908C14CB CRC64;
MFSKKPHGDV KKSTQKVLDT KKDALTRLKH LRIVIENAES IDLKQFFDQH FSHIYYVFFE
NFVTIEASLK QKGHKSQREE LDAILFIFEK ILQLLPERIH QRWQFHSIGL ILKKLLHTGN
SLKIRREGVR LFLLWLQALQ NNCSKEQLWM FSCLIPGFSA PQSEHGPRTL DNLINPPLNL
QETQVTIEEI TPLVPPQSGD KGQEDLTSYF LEALLKYIVI QVKSLEWKNK ENQERGFSFL
FSHFKKYYLP YIFPNICKEN SLYHPILDIP QMRPKPHYVV IKKDAETNEA IYCTKEPFIK
ARVIVIRWLV SFWLEPKPHT GPHIPGMEGE VLPKNIQRAA ASLVSREESK NDNADKTDRT
TEPEQSHSNT STLTEREPSS SSLCSIDEEH LTDIEIVRRV FSSKRSNVNF VTEIFRQAFL
LPICEAAAMR KVVKVYQEWI QQEEKPLFMQ EPEEIVITSS DLPCIENVTD HDISMEEGEK
REEENGTNTA DHVRNSSWAK NGSYQGALHN ASEEATEQNI RAGTQAVLQV FIINSSNIFL
LEPANEIKNL LDEHTDMCKR ILNIYRYMVV QVSMDKKTWE QMLLVLLRVT ESVLKMPSQA
FLQFQGKKNM TLAGRLAGPL FQTLIVAWIK ANLNVYISRE LWDDLLSVLS SLTYWEELAT
EWSLTMETLT KVLARNLYSL DLSDLPLDKL SEQKQKKHKG KGVGHEFQKV SVDKSFSRGW
SRDQPGQAPM RQRSATTTGS PGTEKARSIV RQKTVDIDDA QILPRSTRVR HFSQSEETGN
EVFGALNEEQ PLPRSSSTSD ILEPFTVERA KVNKEDMSQK LPPLNSDIGG SSANVPDLMD
EFIAERLRSG NASTMTRRGS SPGSLEIPKD LPDILNKQNQ MRPIDDPGVP SEWTSPASAG
SSDLISSDSH SDSFSAFQYD GRKFDNFGFG TDTGVTSSAD VDSGSGHHQS AEEQEVASLT
TLHIDSETSS LNQQAFSAEV ATITGSESAS PVHSPLGSRS QTPSPSTLNI DHMEQKDLQL
DEKLHHSVLQ TPDDLEISEF PSECCSVMAG GTLTGWHADV ATVMWRRMLG ILGDVNSIMD
PEIHAQVFDY LCELWQNLAK IRDNLGISTD NLTSPSPPVL IPPLRILTPW LFKATMLTDK
YKQGKLHAYK LICNTMKRRQ DVSPNRDFLT HFYNIMHCGL LHIDQDIVNT IIKHCSPQFF
SLGLPGATML IMDFIVAAGR VASSAFLNAP RVEAQVLLGS LVCFPNLYCE LPSLHPNIPD
VAVSQFTDVK ELIIKTVLSS ARDEPSGPAR CVALCSLGIW ICEELVHESH HPQIKEALNV
ICVSLKFTNK TVAHVACNML HMLVHYVPRL QIYQPDSPLK IIQILIATIT HLLPSTEASS
YEMDKRLVVS LLLCLLDWIM ALPLKTLLQP FHATGAESDK TEKSVLNCIY KVLHGCVYGA
QCFSNPRYFP MSLSDLASVD YDPFMHLESL KEPEPLHSPD SERSSKLQPV TEVKTQMQHG
LISIAARTVI THLVNHLGHY PMSGGPAMLT SQVCENHDNH YSESTELSPE LFESPNIQFF
VLNNTTLVSC IQIRSEENMP GGGLSAGLAS ANSNVRIIVR DLSGKYSWDS AILYGPPPVS
GLSEPTSFML SLSHQEKPEE PPTSNECLED ITVKDGLSLQ FKRFRETVPT WDTIRDEEDV
LDELLQYLGV TSPECLQRTG ISLNIPAPQP VCISEKQEND VINAILKQHT EEKEFVEKHF
NDLNMKAVEQ DEPIPQKPQS AFYYCRLLLS ILGMNSWDKR RSFHLLKKNE KLLRELRNLD
SRQCRETHKI AVFYVAEGQE DKHSILTNTG GSQAYEDFVA GLGWEVNLTN HCGFMGGLQK
NKSTGLTTPY FATSTVEVIF HVSTRMPSDS DDSLTKKLRH LGNDEVHIVW SEHTRDYRRG
IIPTEFGDVL IVIYPMKNHM FSIQIMKKPE VPFFGPLFDG AIVNGKVLPI MVRATAINAS
RALKSLIPLY QNFYEERARY LQTIVQHHLE PTTFEDFAAQ VFSPAPYHHL PSDADH
