ID   RPGFL_HUMAN             Reviewed;         662 AA.
AC   Q9UHV5;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   02-SEP-2008, sequence version 2.
DT   24-JAN-2024, entry version 156.
DE   RecName: Full=Rap guanine nucleotide exchange factor-like 1;
DE   AltName: Full=Link guanine nucleotide exchange factor II;
DE            Short=Link GEFII;
GN   Name=RAPGEFL1;
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] (ISOFORM 2).
RA   Kawasaki H., Chen E.J., Springett G.M., Graybiel A.M., Housman D.E.;
RT   "A new family of Rap guanine nucleotide exchange factors.";
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Tongue;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 1-459 (ISOFORM 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]
RP   STRUCTURE BY NMR OF 314-420.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the RA domain in the human link guanine nucleotide
RT   exchange factor II (Link-GEFII).";
RL   Submitted (SEP-2006) to the PDB data bank.
CC   -!- FUNCTION: Probable guanine nucleotide exchange factor (GEF).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9UHV5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9UHV5-2; Sequence=VSP_035217;
CC       Name=3;
CC         IsoId=Q9UHV5-3; Sequence=VSP_035385, VSP_035386;
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAG36274.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF117946; AAF22003.1; -; mRNA.
DR   EMBL; AK313492; BAG36274.1; ALT_INIT; mRNA.
DR   EMBL; AC068669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC029956; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC115374; AAI15375.1; -; mRNA.
DR   EMBL; BC115375; AAI15376.1; -; mRNA.
DR   CCDS; CCDS11363.2; -. [Q9UHV5-1]
DR   CCDS; CCDS77022.1; -. [Q9UHV5-3]
DR   RefSeq; NP_001290462.1; NM_001303533.1. [Q9UHV5-3]
DR   RefSeq; NP_057423.1; NM_016339.4.
DR   RefSeq; XP_006722000.1; XM_006721937.3.
DR   PDB; 2DHZ; NMR; -; A=314-420.
DR   PDBsum; 2DHZ; -.
DR   AlphaFoldDB; Q9UHV5; -.
DR   BMRB; Q9UHV5; -.
DR   SMR; Q9UHV5; -.
DR   BioGRID; 119369; 6.
DR   IntAct; Q9UHV5; 3.
DR   STRING; 9606.ENSP00000479735; -.
DR   GlyCosmos; Q9UHV5; 2 sites, 1 glycan.
DR   GlyGen; Q9UHV5; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q9UHV5; -.
DR   PhosphoSitePlus; Q9UHV5; -.
DR   BioMuta; RAPGEFL1; -.
DR   DMDM; 205829945; -.
DR   EPD; Q9UHV5; -.
DR   jPOST; Q9UHV5; -.
DR   MassIVE; Q9UHV5; -.
DR   MaxQB; Q9UHV5; -.
DR   PaxDb; 9606-ENSP00000264644; -.
DR   PeptideAtlas; Q9UHV5; -.
DR   ProteomicsDB; 84414; -. [Q9UHV5-1]
DR   ProteomicsDB; 84415; -. [Q9UHV5-2]
DR   ProteomicsDB; 84416; -. [Q9UHV5-3]
DR   Antibodypedia; 16447; 95 antibodies from 21 providers.
DR   DNASU; 51195; -.
DR   Ensembl; ENST00000264644.10; ENSP00000264644.5; ENSG00000108352.13. [Q9UHV5-2]
DR   Ensembl; ENST00000456989.6; ENSP00000394530.2; ENSG00000108352.13. [Q9UHV5-3]
DR   GeneID; 51195; -.
DR   KEGG; hsa:51195; -.
DR   UCSC; uc060exk.1; human. [Q9UHV5-1]
DR   AGR; HGNC:17428; -.
DR   CTD; 51195; -.
DR   DisGeNET; 51195; -.
DR   GeneCards; RAPGEFL1; -.
DR   HGNC; HGNC:17428; RAPGEFL1.
DR   HPA; ENSG00000108352; Tissue enhanced (esophagus, skin, vagina).
DR   neXtProt; NX_Q9UHV5; -.
DR   OpenTargets; ENSG00000108352; -.
DR   PharmGKB; PA134884826; -.
DR   VEuPathDB; HostDB:ENSG00000108352; -.
DR   eggNOG; KOG2378; Eukaryota.
DR   GeneTree; ENSGT00940000160144; -.
DR   HOGENOM; CLU_028002_1_0_1; -.
DR   InParanoid; Q9UHV5; -.
DR   OrthoDB; 5473909at2759; -.
DR   PhylomeDB; Q9UHV5; -.
DR   TreeFam; TF313184; -.
DR   PathwayCommons; Q9UHV5; -.
DR   SignaLink; Q9UHV5; -.
DR   BioGRID-ORCS; 51195; 17 hits in 1148 CRISPR screens.
DR   ChiTaRS; RAPGEFL1; human.
DR   EvolutionaryTrace; Q9UHV5; -.
DR   GenomeRNAi; 51195; -.
DR   Pharos; Q9UHV5; Tdark.
DR   PRO; PR:Q9UHV5; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q9UHV5; Protein.
DR   Bgee; ENSG00000108352; Expressed in lower esophagus mucosa and 144 other cell types or tissues.
DR   ExpressionAtlas; Q9UHV5; baseline and differential.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR   GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR   CDD; cd00155; RasGEF; 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; IPR023578; Ras_GEF_dom_sf.
DR   InterPro; IPR001895; RASGEF_cat_dom.
DR   InterPro; IPR036964; RASGEF_cat_dom_sf.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR23113; GUANINE NUCLEOTIDE EXCHANGE FACTOR; 1.
DR   PANTHER; PTHR23113:SF230; RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR-LIKE 1; 1.
DR   Pfam; PF00617; RasGEF; 1.
DR   SMART; SM00147; RasGEF; 1.
DR   SUPFAM; SSF48366; Ras GEF; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS50009; RASGEF_CAT; 1.
DR   Genevisible; Q9UHV5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Guanine-nucleotide releasing factor;
KW   Reference proteome.
FT   CHAIN           1..662
FT                   /note="Rap guanine nucleotide exchange factor-like 1"
FT                   /id="PRO_0000349202"
FT   DOMAIN          424..660
FT                   /note="Ras-GEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT   REGION          1..149
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..206
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT                   /id="VSP_035217"
FT   VAR_SEQ         1..151
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_035385"
FT   VAR_SEQ         152..174
FT                   /note="EHLLNRVLERLAGGATRDSAASD -> MLIHPRGLPSSSHRRKINSTYFY
FT                   (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_035386"
FT   CONFLICT        81..82
FT                   /note="VP -> PE (in Ref. 4; BC029956)"
FT                   /evidence="ECO:0000305"
FT   STRAND          316..318
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   STRAND          330..332
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   HELIX           338..348
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   STRAND          349..351
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   STRAND          363..368
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   HELIX           383..386
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   STRAND          389..396
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   TURN            398..403
FT                   /evidence="ECO:0007829|PDB:2DHZ"
FT   STRAND          410..413
FT                   /evidence="ECO:0007829|PDB:2DHZ"
SQ   SEQUENCE   662 AA;  73265 MW;  C6724336938D5769 CRC64;
     MKPLEKFLKK QTSQLAGRTV AGGPGGGLGS CGGPGGGGGP GGGGGPAGGQ RSLQRRQSVS
     RLLLPAFLRE PPAEPGLEPP VPEEGGEPAG VAEEPGSGGP CWLQLEEVPG PGPLGGGGPL
     RSPSSYSSDE LSPGEPLTSP PWAPLGAPER PEHLLNRVLE RLAGGATRDS AASDILLDDI
     VLTHSLFLPT EKFLQELHQY FVRAGGMEGP EGLGRKQACL AMLLHFLDTY QGLLQEEEGA
     GHIIKDLYLL IMKDESLYQG LREDTLRLHQ LVETVELKIP EENQPPSKQV KPLFRHFRRI
     DSCLQTRVAF RGSDEIFCRV YMPDHSYVTI RSRLSASVQD ILGSVTEKLQ YSEEPAGRED
     SLILVAVSSS GEKVLLQPTE DCVFTALGIN SHLFACTRDS YEALVPLPEE IQVSPGDTEI
     HRVEPEDVAN HLTAFHWELF RCVHELEFVD YVFHGERGRR ETANLELLLQ RCSEVTHWVA
     TEVLLCEAPG KRAQLLKKFI KIAALCKQNQ DLLSFYAVVM GLDNAAVSRL RLTWEKLPGK
     FKNLFRKFEN LTDPCRNHKS YREVISKMKP PVIPFVPLIL KDLTFLHEGS KTLVDGLVNI
     EKLHSVAEKV RTIRKYRSRP LCLDMEASPN HLQTKAYVRQ FQVIDNQNLL FELSYKLEAN
     SQ
//