P20936 (RASA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras GTPase-activating protein 1
Short name=GAP
Short name=GTPase-activating protein
Short name=RasGAP

Alternative name(s):
Ras p21 protein activator
p120GAP

Gene names

Name:	RASA1
Synonyms:	RASA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1047 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1. Ref.4 Ref.6
Subunit structure	Interacts with SQSTM1. Interacts with SPSB1; the interaction does not promote degradation. Interacts with CAV2 (tyrosine phosphorylated form). Directly interacts with NCK1. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15
Subcellular location	Cytoplasm Ref.4.
Tissue specificity	In placental villi, detected only in the trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not detected in stromal, endothelial or Hofbauer cells (at protein level). Ref.4
Post-translational modification	The N-terminus is blocked. Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits its ability to stimulate the Ras-GTPase activity, whereas phosphorylation by LCK does not display any effect on stimulation activity. Ref.6
Involvement in disease	Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas. Capillary malformation-arteriovenous malformation (CMAVM) [MIM:608354]: Disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Parkes Weber syndrome (PKWS) [MIM:608355]: Disorder characterized by a cutaneous flush with underlying multiple micro-arteriovenous fistulas, in association with soft tissue and skeletal hypertrophy of the affected limb. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Contains 1 C2 domain. Contains 1 PH domain. Contains 1 Ras-GAP domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Proto-oncogene
Domain	Repeat SH2 domain SH3 domain
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cytokinesis Inferred from sequence or structural similarity. Source: UniProtKB embryo development Inferred from sequence or structural similarity. Source: UniProtKB intracellular signal transduction Non-traceable author statement PubMed 1581965. Source: UniProtKB negative regulation of Ras protein signal transduction Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of cell-matrix adhesion Inferred from direct assay PubMed 8344248. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of RNA metabolic process Non-traceable author statement PubMed 9113414. Source: UniProtKB regulation of actin filament polymerization Inferred from direct assay PubMed 8344248. Source: UniProtKB regulation of cell shape Non-traceable author statement PubMed 9113414. Source: UniProtKB vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome intrinsic to internal side of plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome ruffle Inferred from electronic annotation. Source: Compara
Molecular_function	Ras GTPase activator activity Inferred from Biological aspect of Ancestor. Source: RefGenome phospholipid binding Inferred from electronic annotation. Source: InterPro potassium channel inhibitor activity Non-traceable author statement PubMed 1553544. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	6	EBI-1026476,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P20936-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P20936-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-177: Missing.
     178-180: TNQ → MKG

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1047

1047

Ras GTPase-activating protein 1

PRO_0000056636

Regions

Domain

181 – 272

92

SH2 1

Domain

279 – 341

63

SH3

Domain

351 – 441

91

SH2 2

Domain

474 – 577

104

PH

Domain

581 – 676

96

C2

Domain

748 – 942

195

Ras-GAP

Compositional bias

17 – 22

6

Poly-Gly

Compositional bias

135 – 141

7

Poly-Pro

Compositional bias

163 – 168

6

Poly-Glu

Amino acid modifications

Modified residue

615

1

Phosphotyrosine Ref.12

Natural variations

Alternative sequence

1 – 177

177

Missing in isoform 2.

VSP_001625

Alternative sequence

178 – 180

3

TNQ → MKG in isoform 2.

VSP_001626

Natural variant

398

1

R → L in basal cell carcinomas. Ref.20

VAR_002650

Natural variant

400

1

K → E in basal cell carcinomas. Ref.20

VAR_002651

Natural variant

401

1

I → V in basal cell carcinomas. Ref.20

VAR_002652

Natural variant

540

1

C → Y in CMAVM. Ref.21

VAR_017744

Experimental info

Sequence conflict

789

1

R → A AA sequence Ref.4

Secondary structure

1

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1047

Helix Strand Turn

Details...

Beta strand

283 – 288

6

Beta strand

296 – 298

3

Beta strand

306 – 312

7

Beta strand

316 – 322

7

Turn

323 – 325

3

Beta strand

328 – 332

5

Helix

333 – 335

3

Beta strand

336 – 338

3

Helix

346 – 348

3

Beta strand

350 – 352

3

Helix

358 – 366

9

Beta strand

371 – 378

8

Beta strand

380 – 382

3

Beta strand

386 – 391

6

Beta strand

401 – 404

4

Turn

405 – 407

3

Beta strand

408 – 413

6

Helix

419 – 426

8

Helix

720 – 723

4

Helix

724 – 730

7

Helix

736 – 744

9

Beta strand

746 – 748

3

Helix

749 – 762

14

Helix

766 – 780

15

Helix

784 – 786

3

Turn

787 – 789

3

Helix

793 – 805

13

Helix

807 – 823

17

Helix

832 – 834

3

Helix

841 – 860

20

Helix

861 – 865

5

Helix

868 – 884

17

Helix

891 – 900

10

Turn

901 – 904

4

Helix

905 – 910

6

Turn

912 – 916

5

Helix

924 – 941

18

Beta strand

946 – 949

4

Helix

951 – 956

6

Helix

957 – 974

18

Helix

992 – 1004

13

Helix

1006 – 1013

8

Helix

1020 – 1038

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified February 1, 1991. Version 1. Checksum: C35B6567F5BC5370	FASTA	1,047	116,403
	10 20 30 40 50 60 MMAAEAGSEE GGPVTAGAGG GGAAAGSSAY PAVCRVKIPA ALPVAAAPYP GLVETGVAGT 70 80 90 100 110 120 LGGGAALGSE FLGAGSVAGA LGGAGLTGGG TAAGVAGAAA GVAGAAVAGP SGDMALTKLP 130 140 150 160 170 180 TSLLAETLGP GGGFPPLPPP PYLPPLGAGL GTVDEGDSLD GPEYEEEEVA IPLTAPPTNQ 190 200 210 220 230 240 WYHGKLDRTI AEERLRQAGK SGSYLIRESD RRPGSFVLSF LSQMNVVNHF RIIAMCGDYY 250 260 270 280 290 300 IGGRRFSSLS DLIGYYSHVS CLLKGEKLLY PVAPPEPVED RRRVRAILPY TKVPDTDEIS 310 320 330 340 350 360 FLKGDMFIVH NELEDGWMWV TNLRTDEQGL IVEDLVEEVG REEDPHEGKI WFHGKISKQE 370 380 390 400 410 420 AYNLLMTVGQ VCSFLVRPSD NTPGDYSLYF RTNENIQRFK ICPTPNNQFM MGGRYYNSIG 430 440 450 460 470 480 DIIDHYRKEQ IVEGYYLKEP VPMQDQEQVL NDTVDGKEIY NTIRRKTKDA FYKNIVKKGY 490 500 510 520 530 540 LLKKGKGKRW KNLYFILEGS DAQLIYFESE KRATKPKGLI DLSVCSVYVV HDSLFGRPNC 550 560 570 580 590 600 FQIVVQHFSE EHYIFYFAGE TPEQAEDWMK GLQAFCNLRK SSPGTSNKRL RQVSSLVLHI 610 620 630 640 650 660 EEAHKLPVKH FTNPYCNIYL NSVQVAKTHA REGQNPVWSE EFVFDDLPPD INRFEITLSN 670 680 690 700 710 720 KTKKSKDPDI LFMRCQLSRL QKGHATDEWF LLSSHIPLKG IEPGSLRVRA RYSMEKIMPE 730 740 750 760 770 780 EEYSEFKELI LQKELHVVYA LSHVCGQDRT LLASILLRIF LHEKLESLLL CTLNDREISM 790 800 810 820 830 840 EDEATTLFRA TTLASTLMEQ YMKATATQFV HHALKDSILK IMESKQSCEL SPSKLEKNED 850 860 870 880 890 900 VNTNLTHLLN ILSELVEKIF MASEILPPTL RYIYGCLQKS VQHKWPTNTT MRTRVVSGFV 910 920 930 940 950 960 FLRLICPAIL NPRMFNIISD SPSPIAARTL ILVAKSVQNL ANLVEFGAKE PYMEGVNPFI 970 980 990 1000 1010 1020 KSNKHRMIMF LDELGNVPEL PDTTEHSRTD LSRDLAALHE ICVAHSDELR TLSNERGAQQ 1030 1040 HVLKKLLAIT ELLQQKQNQY TKTNDVR
	Isoform 2 (Short) [UniParc]. Checksum: B328E701911065F9	FASTA	870	100,398
	10 20 30 40 50 60 MKGWYHGKLD RTIAEERLRQ AGKSGSYLIR ESDRRPGSFV LSFLSQMNVV NHFRIIAMCG 70 80 90 100 110 120 DYYIGGRRFS SLSDLIGYYS HVSCLLKGEK LLYPVAPPEP VEDRRRVRAI LPYTKVPDTD 130 140 150 160 170 180 EISFLKGDMF IVHNELEDGW MWVTNLRTDE QGLIVEDLVE EVGREEDPHE GKIWFHGKIS 190 200 210 220 230 240 KQEAYNLLMT VGQVCSFLVR PSDNTPGDYS LYFRTNENIQ RFKICPTPNN QFMMGGRYYN 250 260 270 280 290 300 SIGDIIDHYR KEQIVEGYYL KEPVPMQDQE QVLNDTVDGK EIYNTIRRKT KDAFYKNIVK 310 320 330 340 350 360 KGYLLKKGKG KRWKNLYFIL EGSDAQLIYF ESEKRATKPK GLIDLSVCSV YVVHDSLFGR 370 380 390 400 410 420 PNCFQIVVQH FSEEHYIFYF AGETPEQAED WMKGLQAFCN LRKSSPGTSN KRLRQVSSLV 430 440 450 460 470 480 LHIEEAHKLP VKHFTNPYCN IYLNSVQVAK THAREGQNPV WSEEFVFDDL PPDINRFEIT 490 500 510 520 530 540 LSNKTKKSKD PDILFMRCQL SRLQKGHATD EWFLLSSHIP LKGIEPGSLR VRARYSMEKI 550 560 570 580 590 600 MPEEEYSEFK ELILQKELHV VYALSHVCGQ DRTLLASILL RIFLHEKLES LLLCTLNDRE 610 620 630 640 650 660 ISMEDEATTL FRATTLASTL MEQYMKATAT QFVHHALKDS ILKIMESKQS CELSPSKLEK 670 680 690 700 710 720 NEDVNTNLTH LLNILSELVE KIFMASEILP PTLRYIYGCL QKSVQHKWPT NTTMRTRVVS 730 740 750 760 770 780 GFVFLRLICP AILNPRMFNI ISDSPSPIAA RTLILVAKSV QNLANLVEFG AKEPYMEGVN 790 800 810 820 830 840 PFIKSNKHRM IMFLDELGNV PELPDTTEHS RTDLSRDLAA LHEICVAHSD ELRTLSNERG 850 860 870 AQQHVLKKLL AITELLQQKQ NQYTKTNDVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of two types of GAP complementary DNA from human placenta." Trahey M., Wong G., Halenbeck R., Rubinfeld B., Martin G.A., Ladner M., Long C.M., Crosier W.J., Watt K., Koths K., McCormick F. Science 242:1697-1700(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Placenta.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"Purification, characterization, and cellular localization of the 100-kDa human placental GTPase-activating protein." Zhang Y., Zhang G., Mollat P., Carles C., Riva M., Frobert Y., Malassine A., Rostene W., Thang D.C., Beltchev B., Tavitian A., Thane M.N. J. Biol. Chem. 268:18875-18881(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 294-303; 326-334; 392-398; 439-457; 458-466; 479-483; 777-790 AND 821-825, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Placenta.
[5]	"Purification, characterization, and western blot analysis of human GTPase-activating protein from native and recombinant sources." Halenbeck R., Crosier W.J., Clark R., McCormick F., Koths K. J. Biol. Chem. 265:21922-21928(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-7 (ISOFORM 2).
[6]	"Differential actions of p60c-Src and Lck kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm." Giglione C., Gonfloni S., Parmeggiani A. Eur. J. Biochem. 268:3275-3283(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, FUNCTION.
[7]	"GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit." Kazlauskas A., Kashishian A., Cooper J.A., Valius M. Mol. Cell. Biol. 12:2534-2544(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDGFRB.
[8]	"Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region." Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J. Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1.
[9]	"Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho-caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated with lipid rafts/caveolae, but no longer forms a high molecular mass hetero-oligomer with caveolin-1." Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., Lisanti M.P. J. Biol. Chem. 277:34556-34567(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV2.
[10]	"Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27)." Wang X.B., Lee H., Capozza F., Marmon S., Sotgia F., Brooks J.W., Campos-Gonzalez R., Lisanti M.P. Biochemistry 43:13694-13706(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAV2.
[11]	"The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway." Wang D., Li Z., Messing E.M., Wu G. J. Biol. Chem. 280:16393-16401(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPSB1.
[12]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-615, MASS SPECTROMETRY.
[13]	"Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src involves tyrosine phosphorylation of PDK1 and Src homology 2 domain binding." Yang K.J., Shin S., Piao L., Shin E., Li Y., Park K.A., Byun H.S., Won M., Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., Brazil D.P., Hemmings B.A., Park J. J. Biol. Chem. 283:1480-1491(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDPK1.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and regulates its activity." Ger M., Zitkus Z., Valius M. Cell. Signal. 23:1651-1658(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCK1.
[16]	"Solution structure of GAP SH3 domain by 1H NMR and spatial arrangement of essential Ras signaling-involved sequence." Yang Y.S., Garbay C., Duschesne M., Cornille F., Jullian N., Fromage N., Tocque B., Roques B.P. EMBO J. 13:1270-1279(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 275-350.
[17]	"Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras." Scheffzek K., Lautwein A., Kabsch W., Reza Ahmadian M., Wittinghofer A. Nature 384:591-596(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 714-1047.
[18]	"The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants." Scheffzek K., Ahmadian M.R., Kabsch W., Wiesmuller L., Lautwein A., Schmitz F., Wittinghofer A. Science 277:333-338(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 714-1047 IN COMPLEX WITH RAS.
[19]	"Solution structure of the SH3 domain and of the second SH2 domain of human RAS GTPase-activating protein 1." RIKEN structural genomics initiative (RSGI) Submitted (MAY-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 282-446.
[20]	"Nonsense mutations in the C-terminal SH2 region of the GTPase activating protein (GAP) gene in human tumours." Friedman E., Gejman P.V., Martin G.A., McCormick F. Nat. Genet. 5:242-247(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LEU-398; GLU-400 AND VAL-401.
[21]	"Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations." Eerola I., Boon L.M., Mulliken J.B., Burrows P.E., Dompmartin A., Watanabe S., Vanwijck R., Vikkula M. Am. J. Hum. Genet. 73:1240-1249(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CMAVM TYR-540.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M23379 mRNA. Translation: AAA52517.1.
M23612 mRNA. Translation: AAA35865.1.
AK312739 mRNA. Translation: BAG35610.1.
BC033015 mRNA. Translation: AAH33015.1.

IPI

IPI00026262.
IPI00220356.

PIR

A40121.
B40121.

RefSeq

NP_002881.1. NM_002890.2.
NP_072179.1. NM_022650.2.

UniGene

Hs.664080.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WER	X-ray	1.60	A	714-1047	[»]
1WQ1	X-ray	2.50	G	714-1047	[»]
2GQI	NMR	-	A	282-339	[»]
2GSB	NMR	-	A	341-446	[»]
2J05	X-ray	1.50	A/B	281-341	[»]
2J06	X-ray	1.80	A/B	281-341	[»]
4FSS	X-ray	2.25	A/B/C	281-341	[»]

ProteinModelPortal

P20936.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-144N.

IntAct

P20936. 8 interactions.

MINT

MINT-195165.

STRING

9606.ENSP00000274376.

PTM databases

PhosphoSite

P20936.

Polymorphism databases

DMDM

121743.

Proteomic databases

PaxDb

P20936.

PRIDE

P20936.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274376; ENSP00000274376; ENSG00000145715.
ENST00000456692; ENSP00000411221; ENSG00000145715.

GeneID

5921.

KEGG

hsa:5921.

UCSC

uc003kiw.3. human.
uc003kix.3. human.

Organism-specific databases

CTD

5921.

GeneCards

GC05P086565.

HGNC

HGNC:9871. RASA1.

HPA

CAB007789.

MIM

139150. gene.
608354. phenotype.
608355. phenotype.

neXtProt

NX_P20936.

Orphanet

137667. Capillary malformation-arteriovenous malformation.
90307. Parkes Weber syndrome.

PharmGKB

PA34232.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG282054.

HOGENOM

HOG000007794.

HOVERGEN

HBG057470.

InParanoid

P20936.

KO

K04352.

OMA

CLQNLAN.

OrthoDB

EOG4GMTW7.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
aurora_a_pathway. Aurora A signaling.
aurora_b_pathway. Aurora B signaling.
bcr_5pathway. BCR signaling pathway.
ephbfwdpathway. EPHB forward signaling.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
il2_1pathway. IL2-mediated signaling events.
insulin_pathway. Insulin Pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
pdgfrbpathway. PDGFR-beta signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P20936.

Bgee

P20936.

CleanEx

HS_RASA1.

Genevestigator

P20936.

GermOnline

ENSG00000145715. Homo sapiens.

Family and domain databases

Gene3D

1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
3.30.505.10. 2 hits.

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001936. RasGAP.
IPR023152. RasGAP_CS.
IPR008936. Rho_GTPase_activation_prot.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00168. C2. 1 hit.
PF00169. PH. 1 hit.
PF00616. RasGAP. 1 hit.
PF00017. SH2. 2 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00239. C2. 1 hit.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF48350. Rho_GAP. 1 hit.

PROSITE

PS50004. C2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

RASA1. human.

EvolutionaryTrace

P20936.

GenomeRNAi

5921.

NextBio

23056.

PMAP-CutDB

P20936.

SOURCE

Search...

Entry information

Entry name

RASA1_HUMAN

Accession

Primary (citable) accession number: P20936
Secondary accession number(s): B2R6W3, Q9UDI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 164 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.