NGAP_HUMAN
ID NGAP_HUMAN Reviewed; 1139 AA.
AC Q9UJF2; F8W755; O95174; Q2TB22; Q5TFU9;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Ras GTPase-activating protein nGAP;
DE AltName: Full=RAS protein activator-like 2;
GN Name=RASAL2; Synonyms=NGAP;
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 1).
RC TISSUE=Heart;
RX PubMed=9877179; DOI=10.1016/s0014-5793(98)01530-0;
RA Noto S., Maeda T., Hattori S., Inazawa J., Imamura M., Asaka M.,
RA Hatakeyama M.;
RT "A novel human RasGAP-like gene that maps within the prostate cancer
RT susceptibility locus at chromosome 1q25.";
RL FEBS Lett. 441:127-131(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-1139 (ISOFORM 2).
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-89 AND SER-663, AND
RP IDENTIFICATION BY 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-864, AND IDENTIFICATION BY
RP 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-620 AND SER-663, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND IDENTIFICATION BY
RP 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 [11]
RP VARIANTS [LARGE SCALE ANALYSIS] TRP-165 AND ASP-379.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway.
CC -!- INTERACTION:
CC Q9UJF2; Q96PC5: MIA2; NbExp=3; IntAct=EBI-359444, EBI-1050253;
CC Q9UJF2; Q13077: TRAF1; NbExp=3; IntAct=EBI-359444, EBI-359224;
CC Q9UJF2; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-359444, EBI-739895;
CC Q9UJF2; PRO_0000037548 [Q9WMX2]; Xeno; NbExp=2; IntAct=EBI-359444, EBI-6863741;
CC Q9UJF2-2; P23508: MCC; NbExp=3; IntAct=EBI-12171247, EBI-307531;
CC Q9UJF2-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12171247, EBI-16439278;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UJF2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJF2-2; Sequence=VSP_045777, VSP_045778;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI10612.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF047711; AAD04814.1; -; mRNA.
DR EMBL; AL035702; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365357; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL499617; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110611; AAI10612.1; ALT_INIT; mRNA.
DR CCDS; CCDS1321.2; -. [Q9UJF2-2]
DR CCDS; CCDS1322.1; -. [Q9UJF2-1]
DR RefSeq; NP_004832.1; NM_004841.3. [Q9UJF2-1]
DR RefSeq; NP_733793.2; NM_170692.2. [Q9UJF2-2]
DR AlphaFoldDB; Q9UJF2; -.
DR SMR; Q9UJF2; -.
DR BioGRID; 114848; 141.
DR CORUM; Q9UJF2; -.
DR DIP; DIP-27570N; -.
DR IntAct; Q9UJF2; 29.
DR MINT; Q9UJF2; -.
DR STRING; 9606.ENSP00000356621; -.
DR GlyGen; Q9UJF2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UJF2; -.
DR PhosphoSitePlus; Q9UJF2; -.
DR BioMuta; RASAL2; -.
DR DMDM; 13959419; -.
DR EPD; Q9UJF2; -.
DR jPOST; Q9UJF2; -.
DR MassIVE; Q9UJF2; -.
DR MaxQB; Q9UJF2; -.
DR PaxDb; Q9UJF2; -.
DR PeptideAtlas; Q9UJF2; -.
DR PRIDE; Q9UJF2; -.
DR ProteomicsDB; 29892; -.
DR ProteomicsDB; 84621; -. [Q9UJF2-1]
DR Antibodypedia; 20575; 161 antibodies from 29 providers.
DR DNASU; 9462; -.
DR Ensembl; ENST00000367649.8; ENSP00000356621.3; ENSG00000075391.17. [Q9UJF2-2]
DR Ensembl; ENST00000462775.5; ENSP00000420558.1; ENSG00000075391.17. [Q9UJF2-1]
DR GeneID; 9462; -.
DR KEGG; hsa:9462; -.
DR MANE-Select; ENST00000367649.8; ENSP00000356621.3; NM_170692.4; NP_733793.2. [Q9UJF2-2]
DR UCSC; uc001glq.4; human. [Q9UJF2-1]
DR CTD; 9462; -.
DR DisGeNET; 9462; -.
DR GeneCards; RASAL2; -.
DR HGNC; HGNC:9874; RASAL2.
DR HPA; ENSG00000075391; Tissue enhanced (retina).
DR MIM; 606136; gene.
DR neXtProt; NX_Q9UJF2; -.
DR OpenTargets; ENSG00000075391; -.
DR PharmGKB; PA34235; -.
DR VEuPathDB; HostDB:ENSG00000075391; -.
DR eggNOG; KOG3508; Eukaryota.
DR GeneTree; ENSGT00940000157702; -.
DR HOGENOM; CLU_001727_1_0_1; -.
DR InParanoid; Q9UJF2; -.
DR OMA; SIMHDVP; -.
DR OrthoDB; 69536at2759; -.
DR PhylomeDB; Q9UJF2; -.
DR TreeFam; TF105303; -.
DR PathwayCommons; Q9UJF2; -.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q9UJF2; -.
DR BioGRID-ORCS; 9462; 7 hits in 1074 CRISPR screens.
DR ChiTaRS; RASAL2; human.
DR GeneWiki; RASAL2; -.
DR GenomeRNAi; 9462; -.
DR Pharos; Q9UJF2; Tbio.
DR PRO; PR:Q9UJF2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UJF2; protein.
DR Bgee; ENSG00000075391; Expressed in buccal mucosa cell and 177 other tissues.
DR ExpressionAtlas; Q9UJF2; baseline and differential.
DR Genevisible; Q9UJF2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:2000257; P:regulation of protein activation cascade; IEA:Ensembl.
DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 1.10.506.10; -; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR021887; DAB2P_C.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039360; Ras_GTPase.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR PANTHER; PTHR10194; PTHR10194; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF12004; DUF3498; 1.
DR Pfam; PF00616; RasGAP; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; GTPase activation; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1139
FT /note="Ras GTPase-activating protein nGAP"
FT /id="PRO_0000056653"
FT DOMAIN 41..158
FT /note="PH"
FT DOMAIN 149..267
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 327..519
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..782
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 803..869
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 910..953
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 72..87
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 803..835
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 836..854
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 911..953
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 620
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1..4
FT /note="MQTP -> MELSPSSGGAAEALSWPEMFPALESDSPLPPEDLDAVVPVSGAV
FT AGGMLDRILLESVCQQQSWVRVYDVKGPPTHRLSCGQSPYTETTTWERKYCILTDSQLV
FT LLNKEKEIPVEGGQEQQTDSTKGRCLRRTVSVPSEGQFPEYPPEGATKL (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045777"
FT VAR_SEQ 590..596
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045778"
FT VARIANT 165
FT /note="R -> W (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs765646105)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035541"
FT VARIANT 379
FT /note="E -> D (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035542"
SQ SEQUENCE 1139 AA; 128558 MW; 4A65C8243E1259A3 CRC64;
MQTPEVPAER SPRRRSISGT STSEKPNSMD TANTSPFKVP GFFSKRLKGS IKRTKSQSKL
DRNTSFRLPS LRSTDDRSRG LPKLKESRSH ESLLSPCSTV ECLDLGRGEP VSVKPLHSSI
LGQDFCFEVT YLSGSKCFSC NSASERDKWM ENLRRTVQPN KDNCRRAENV LRLWIIEAKD
LAPKKKYFCE LCLDDTLFAR TTSKTKADNI FWGEHFEFFS LPPLHSITVH IYKDVEKKKK
KDKNNYVGLV NIPTASVTGR QFVEKWYPVS TPTPNKGKTG GPSIRIKSRF QTITILPMEQ
YKEFAEFVTS NYTMLCSVLE PVISVRNKEE LACALVHILQ STGRAKDFLT DLVMSEVDRC
GEHDVLIFRE NTIATKSIEE YLKLVGQQYL HDALGEFIKA LYESDENCEV DPSKCSSSEL
IDHQSNLKMC CELAFCKIIN SYCVFPRELK EVFASWKQQC LNRGKQDISE RLISASLFLR
FLCPAIMSPS LFNLMQEYPD DRTSRTLTLI AKVIQNLANF AKFGNKEEYM AFMNDFLEHE
WGGMKRFLLE ISNPDTISNT PGFDGYIDLG RELSVLHSLL WEVVSQLDKG ENSFLQATVA
KLGPLPRVLA DITKSLTNPT PIQQQLRRFT EHNSSPNVSG SLSSGLQKIF EDPTDSDLHK
LKSPSQDNTD SYFRGKTLLL VQQASSQSMT YSEKDERESS LPNGRSVSLM DLQDTHAAQV
EHASVMLDVP IRLTGSQLSI TQVASIKQLR ETQSTPQSAP QVRRPLHPAL NQPGGLQPLS
FQNPVYHLNN PIPAMPKASI DSSLENLSTA SSRSQSNSED FKLSGPSNSS MEDFTKRSTQ
SEDFSRRHTV PDRHIPLALP RQNSTGQAQI RKVDQGGLGA RAKAPPSLPH SASLRSTGSM
SVVSAALVAE PVQNGSRSRQ QSSSSRESPV PKVRAIQRQQ TQQVQSPVDS ATMSPVERTA
AWVLNNGQYE EDVEETEQNL DEAKHAEKYE QEITKLKERL RVSSRRLEEY ERRLLVQEQQ
MQKLLLEYKA RLEDSEERLR RQQEEKDSQM KSIISRLMAV EEELKKDHAE MQAVIDAKQK
IIDAQEKRIV SLDSANTRLM SALTQVKERY SMQVRNGISP TNPTKLSITE NGEFKNSSC
