ID   RGF1A_HUMAN             Reviewed;         481 AA.
AC   Q8N9B8; Q8TBF1;
DT   21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-AUG-2007, sequence version 2.
DT   02-SEP-2026, entry version 153.
DE   RecName: Full=Ras-GEF domain-containing family member 1A;
GN   Name=RASGEF1A;
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).
RC   TISSUE=Substantia nigra;
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   [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   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=17121879; DOI=10.1158/1078-0432.ccr-06-0783;
RA   Ura K., Obama K., Satoh S., Sakai Y., Nakamura Y., Furukawa Y.;
RT   "Enhanced RASGEF1A expression is involved in the growth and migration of
RT   intrahepatic cholangiocarcinoma.";
RL   Clin. Cancer Res. 12:6611-6616(2006).
RN   [4]
RP   FUNCTION.
RX   PubMed=19645719; DOI=10.1111/j.1742-4658.2009.07166.x;
RA   Yaman E., Gasper R., Koerner C., Wittinghofer A., Tazebay U.H.;
RT   "RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that
RT   discriminate between Rap GTP-binding proteins and mediate Rap2-specific
RT   nucleotide exchange.";
RL   FEBS J. 276:4607-4616(2009).
CC   -!- FUNCTION: Guanine nucleotide exchange factor (GEF) with specificity for
CC       RAP2A, KRAS, HRAS, and NRAS (in vitro). Plays a role in cell migration.
CC       {ECO:0000269|PubMed:17121879, ECO:0000269|PubMed:19645719}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8N9B8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N9B8-2; Sequence=VSP_027312;
CC   -!- TISSUE SPECIFICITY: Detected in brain and spinal cord. Highly expressed
CC       in a number of intrahepatic cholangiocarcinoma tissue biopsies.
CC       {ECO:0000269|PubMed:17121879}.
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DR   EMBL; AK095136; BAC04491.1; -; mRNA.
DR   EMBL; BC022548; AAH22548.2; -; mRNA.
DR   CCDS; CCDS60517.1; -. [Q8N9B8-2]
DR   CCDS; CCDS7202.2; -. [Q8N9B8-1]
DR   RefSeq; NP_001269791.1; NM_001282862.2. [Q8N9B8-2]
DR   RefSeq; NP_660356.2; NM_145313.4. [Q8N9B8-1]
DR   AlphaFoldDB; Q8N9B8; -.
DR   SMR; Q8N9B8; -.
DR   BioGRID; 128673; 9.
DR   FunCoup; Q8N9B8; 699.
DR   IntAct; Q8N9B8; 5.
DR   NDEx; IQUERY-CP-RASGEF1A; 1 NDEx IQuery Curated Pathway.
DR   STRING; 9606.ENSP00000363583; -.
DR   iPTMnet; Q8N9B8; -.
DR   PhosphoSitePlus; Q8N9B8; -.
DR   BioMuta; RASGEF1A; -.
DR   DMDM; 156633608; -.
DR   MassIVE; Q8N9B8; -.
DR   PaxDb; 9606-ENSP00000363583; -.
DR   PeptideAtlas; Q8N9B8; -.
DR   ProteomicsDB; 72520; -. [Q8N9B8-1]
DR   ProteomicsDB; 72521; -. [Q8N9B8-2]
DR   Antibodypedia; 26875; 79 antibodies from 25 providers.
DR   DNASU; 221002; -.
DR   Ensembl; ENST00000374459.5; ENSP00000363583.1; ENSG00000198915.13. [Q8N9B8-2]
DR   Ensembl; ENST00000395809.5; ENSP00000379154.1; ENSG00000198915.13. [Q8N9B8-1]
DR   Ensembl; ENST00000395810.6; ENSP00000379155.1; ENSG00000198915.13. [Q8N9B8-1]
DR   Ensembl; ENST00000898232.1; ENSP00000568291.1; ENSG00000198915.13. [Q8N9B8-1]
DR   Ensembl; ENST00000898233.1; ENSP00000568292.1; ENSG00000198915.13. [Q8N9B8-1]
DR   GeneID; 221002; -.
DR   KEGG; hsa:221002; -.
DR   MANE-Select; ENST00000395810.6; ENSP00000379155.1; NM_145313.4; NP_660356.2.
DR   UCSC; uc001jao.3; human. [Q8N9B8-1]
DR   AGR; HGNC:24246; -.
DR   ClinPGx; PA134884893; -.
DR   CTD; 221002; -.
DR   DisGeNET; 221002; -.
DR   GeneCards; RASGEF1A; -.
DR   HGNC; HGNC:24246; RASGEF1A.
DR   HPA; ENSG00000198915; Tissue enhanced (bone marrow, brain).
DR   MalaCards; RASGEF1A; -.
DR   MIM; 614531; gene.
DR   OpenTargets; ENSG00000198915; -.
DR   VEuPathDB; HostDB:ENSG00000198915; -.
DR   eggNOG; KOG3541; Eukaryota.
DR   GeneTree; ENSGT00940000160822; -.
DR   HOGENOM; CLU_022907_2_0_1; -.
DR   InParanoid; Q8N9B8; -.
DR   OrthoDB; 20825at2759; -.
DR   PAN-GO; Q8N9B8; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; Q8N9B8; -.
DR   PathwayCommons; Q8N9B8; -.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   SignaLink; Q8N9B8; -.
DR   SIGNOR; Q8N9B8; -.
DR   Agora; ENSG00000198915; -.
DR   BioGRID-ORCS; 221002; 12 hits in 1152 CRISPR screens.
DR   GenomeRNAi; 221002; -.
DR   Pharos; Q8N9B8; Tdark.
DR   PRO; PR:Q8N9B8; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q8N9B8; protein.
DR   Bgee; ENSG00000198915; Expressed in endothelial cell and 155 other cell types or tissues.
DR   ExpressionAtlas; Q8N9B8; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR   GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR   GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:FlyBase.
DR   GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR   CDD; cd00155; RasGEF; 1.
DR   CDD; cd06224; REM; 1.
DR   FunFam; 1.10.840.10:FF:000008; Ras-GEF domain-containing family member 1B; 1.
DR   FunFam; 1.20.870.10:FF:000007; Ras-GEF domain-containing family member 1B; 1.
DR   Gene3D; 1.10.840.10; Ras guanine-nucleotide exchange factors catalytic domain; 1.
DR   Gene3D; 1.20.870.10; Son of sevenless (SoS) protein Chain: S domain 1; 1.
DR   InterPro; IPR008937; Ras-like_GEF.
DR   InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR   InterPro; IPR023578; Ras_GEF_dom_sf.
DR   InterPro; IPR001895; RASGEF_cat_dom.
DR   InterPro; IPR036964; RASGEF_cat_dom_sf.
DR   PANTHER; PTHR23113; GUANINE NUCLEOTIDE EXCHANGE FACTOR; 1.
DR   PANTHER; PTHR23113:SF172; RAS-GEF DOMAIN-CONTAINING FAMILY MEMBER 1A; 1.
DR   Pfam; PF00617; RasGEF; 1.
DR   Pfam; PF00618; RasGEF_N; 1.
DR   SMART; SM00147; RasGEF; 1.
DR   SMART; SM00229; RasGEFN; 1.
DR   SUPFAM; SSF48366; Ras GEF; 1.
DR   PROSITE; PS50009; RASGEF_CAT; 1.
DR   PROSITE; PS50212; RASGEF_NTER; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Guanine-nucleotide releasing factor;
KW   Proteomics identification; Reference proteome.
FT   CHAIN           1..481
FT                   /note="Ras-GEF domain-containing family member 1A"
FT                   /id="PRO_0000297635"
FT   DOMAIN          41..170
FT                   /note="N-terminal Ras-GEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT   DOMAIN          214..461
FT                   /note="Ras-GEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT   VAR_SEQ         1
FT                   /note="M -> MFLEPQETM (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_027312"
FT   CONFLICT        465
FT                   /note="M -> V (in Ref. 2; AAH22548)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   481 AA;  54556 MW;  CF827AAC588525C0 CRC64;
     MPQTSVVFSS ILGPSCSGQV QPGMGERGGG AGGGSGDLIF QDGHLISGSL EALMEHLVPT
     VDYYPDRTYI FTFLLSSRVF MPPHDLLARV GQICVEQKQQ LEAGPEKAKL KSFSAKIVQL
     LKEWTEAFPY DFQDEKAMAE LKAITHRVTQ CDEENGTVKK AIAQMTQSLL LSLAARSQLQ
     ELREKLRPPA VDKGPILKTK PPAAQKDILG VCCDPLVLAQ QLTHIELDRV SSIYPEDLMQ
     IVSHMDSLDN HRCRGDLTKT YSLEAYDNWF NCLSMLVATE VCRVVKKKHR TRMLEFFIDV
     ARECFNIGNF NSMMAIISGM NLSPVARLKK TWSKVKTAKF DVLEHHMDPS SNFCNYRTAL
     QGATQRSQMA NSSREKIVIP VFNLFVKDIY FLHKIHTNHL PNGHINFKKF WEISRQIHEF
     MTWTQVECPF EKDKKIQSYL LTAPIYSEEA LFVASFESEG PENHMEKDSW KTLRTTLLNR
     A
//