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O43374 (RASL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras GTPase-activating protein 4
Alternative name(s):
Calcium-promoted Ras inactivator
Ras p21 protein activator 4
RasGAP-activating-like protein 2
Gene names
Name:RASA4
Synonyms:CAPRI, GAPL, KIAA0538
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length803 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Ca2+-dependent Ras GTPase-activating protein, that switches off the Ras-MAPK pathway following a stimulus that elevates intracellular calcium. Functions as an adaptor for Cdc42 and Rac1 during FcR-mediated phagocytosis. Ref.1

Subcellular location

Cytoplasmcytosol. Cell membrane; Peripheral membrane protein. Note: Localized to the cytosol as a result of its lack of phosphoinositide binding activity. Upon agonist-stimulated calcium mobilization, utilizes the C2A and C2B domains to associate with the plasma membrane. Ref.1

Tissue specificity

Widely expressed. Ref.1

Domain

The PH domain does not bind phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate. This lack of binding activity is due to Leu-592, compared to Arg found in other family members.

Sequence similarities

Contains 1 Btk-type zinc finger.

Contains 2 C2 domains.

Contains 1 PH domain.

Contains 1 Ras-GAP domain.

Sequence caution

The sequence AAB97935.2 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAP22345.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence BAA25464.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43374-1)

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: O43374-2)

The sequence of this isoform differs from the canonical sequence as follows:
     611-656: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 803803Ras GTPase-activating protein 4
PRO_0000056647

Regions

Domain1 – 8888C2 1
Domain129 – 21688C2 2
Domain302 – 512211Ras-GAP
Domain566 – 673108PH
Zinc finger675 – 71137Btk-type
Compositional bias500 – 5034Poly-Leu

Natural variations

Alternative sequence611 – 65646Missing in isoform 2.
VSP_039965
Natural variant3521M → V. Ref.1 Ref.5
Corresponds to variant rs746316 [ dbSNP | Ensembl ].
VAR_027680
Natural variant4321R → P.
Corresponds to variant rs886346 [ dbSNP | Ensembl ].
VAR_027681
Natural variant7311Y → C.
Corresponds to variant rs1060228 [ dbSNP | Ensembl ].
VAR_027682

Experimental info

Sequence conflict2131G → V in AK026441. Ref.3
Sequence conflict2601D → G in AK026441. Ref.3
Sequence conflict4291R → L in AK026441. Ref.3
Sequence conflict4801M → V in AK026441. Ref.3
Sequence conflict6061T → M in BAA25464. Ref.2
Sequence conflict7521A → T in BAA25464. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 15, 2003. Version 2.
Checksum: 6E70DBF2F8F5D0E9

FASTA80390,458
        10         20         30         40         50         60 
MAKRSSLYIR IVEGKNLPAK DITGSSDPYC IVKVDNEPII RTATVWKTLC PFWGEEYQVH 

        70         80         90        100        110        120 
LPPTFHAVAF YVMDEDALSR DDVIGKVCLT RDTIASHPKG FSGWAHLTEV DPDEEVQGEI 

       130        140        150        160        170        180 
HLRLEVWPGA RACRLRCSVL EARDLAPKDR NGTSDPFVRV RYKGRTRETS IVKKSCYPRW 

       190        200        210        220        230        240 
NETFEFELQE GAMEALCVEA WDWDLVSRND FLGKVVIDVQ RLRVVQQEEG WFRLQPDQSK 

       250        260        270        280        290        300 
SRRHDEGNLG SLQLEVRLRD ETVLPSSYYQ PLVHLLCHEV KLGMQGPGQL IPLIEETTST 

       310        320        330        340        350        360 
ECRQDVATNL LKLFLGQGLA KDFLDLLFQL ELSRTSETNT LFRSNSLASK SMESFLKVAG 

       370        380        390        400        410        420 
MQYLHGVLGP IINKVFEEKK YVELDPSKVE VKDVGCSGLH RPQTEAEVLE QSAQTLRAHL 

       430        440        450        460        470        480 
GALLSALSRS VRACPAVVRA TFRQLFRRVR ERFPGAQHEN VPFIAVTSFL CLRFFSPAIM 

       490        500        510        520        530        540 
SPKLFHLRER HADARTSRTL LLLAKAVQNV GNMDTPASRA KEAWMEPLQP TVRQGVAQLK 

       550        560        570        580        590        600 
DFITKLVDIE EKDELDLQRT LSLQAPPVKE GPLFIHRTKG KGPLMSSSFK KLYFSLTTEA 

       610        620        630        640        650        660 
LSFAKTPSSK KSALIKLANI RAAEKVEEKS FGGSHVMQVI YTDDAGRPQT AYLQCKCVNE 

       670        680        690        700        710        720 
LNQWLSALRK VSINNTGLLG SYHPGVFRGD KWSCCHQKEK TGQGCDKTRS RVTLQEWNDP 

       730        740        750        760        770        780 
LDHDLEAQLI YRHLLGVEAM LWERHRELSG GAEAGTVPTS PGKVPEDSLA RLLRVLQDLR 

       790        800 
EAHSSSPAGS PPSEPNCLLE LQT 

« Hide

Isoform 2 [UniParc].

Checksum: EEBA12E7214670AB
Show »

FASTA75785,409

References

« Hide 'large scale' references
[1]"CAPRI regulates Ca(2+)-dependent inactivation of the Ras-MAPK pathway."
Lockyer P.J., Kupzig S., Cullen P.J.
Curr. Biol. 11:981-986(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-352, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Blood.
[2]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"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. expand/collapse author list , 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).
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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), VARIANT VAL-352.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY029206 mRNA. Translation: AAK31582.1.
AB011110 mRNA. Translation: BAA25464.2. Different initiation.
AK026441 mRNA. No translation available.
AC004084 Genomic DNA. Translation: AAB97935.2. Sequence problems.
AC093668 Genomic DNA. No translation available.
AC105052 Genomic DNA. Translation: AAP22345.1. Sequence problems.
BC113663 mRNA. Translation: AAI13664.1.
CCDSCCDS47674.1. [O43374-2]
CCDS5725.1. [O43374-1]
RefSeqNP_001073346.2. NM_001079877.2. [O43374-2]
NP_008920.5. NM_006989.5. [O43374-1]
UniGeneHs.530089.
Hs.656696.

3D structure databases

ProteinModelPortalO43374.
SMRO43374. Positions 3-562, 573-707.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115458. 3 interactions.
IntActO43374. 4 interactions.
MINTMINT-1370707.
STRING9606.ENSP00000262940.

PTM databases

PhosphoSiteO43374.

Proteomic databases

MaxQBO43374.
PaxDbO43374.
PRIDEO43374.

Protocols and materials databases

DNASU10156.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262940; ENSP00000262940; ENSG00000105808. [O43374-1]
ENST00000449970; ENSP00000412876; ENSG00000105808. [O43374-2]
GeneID10156.
KEGGhsa:10156.
UCSCuc003vae.3. human. [O43374-1]
uc010lih.2. human. [O43374-2]

Organism-specific databases

CTD10156.
GeneCardsGC07M102220.
H-InvDBHIX0034020.
HIX0201129.
HGNCHGNC:23181. RASA4.
HPAHPA043010.
MIM607943. gene.
neXtProtNX_O43374.
PharmGKBPA134889495.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5038.
HOGENOMHOG000234324.
HOVERGENHBG106587.
InParanoidO43374.
KOK17630.
OMAEVKLGTQ.
OrthoDBEOG7J17Z6.
PhylomeDBO43374.
TreeFamTF105302.

Gene expression databases

BgeeO43374.
CleanExHS_RASA4.
GenevestigatorO43374.

Family and domain databases

Gene3D1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 2 hits.
4.10.1130.10. 1 hit.
InterProIPR000008. C2_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001936. RasGAP.
IPR023152. RasGAP_CS.
IPR008936. Rho_GTPase_activation_prot.
IPR001562. Znf_Btk_motif.
[Graphical view]
PfamPF00779. BTK. 1 hit.
PF00168. C2. 2 hits.
PF00616. RasGAP. 1 hit.
[Graphical view]
PRINTSPR00360. C2DOMAIN.
SMARTSM00107. BTK. 1 hit.
SM00239. C2. 2 hits.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 2 hits.
PROSITEPS50004. C2. 2 hits.
PS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
PS51113. ZF_BTK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRASA4. human.
GeneWikiRASA4.
GenomeRNAi10156.
NextBio38444.
PROO43374.
SOURCESearch...

Entry information

Entry nameRASL2_HUMAN
AccessionPrimary (citable) accession number: O43374
Secondary accession number(s): O60286 expand/collapse secondary AC list , Q14CQ4, Q86UW3, Q96QU0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: August 15, 2003
Last modified: July 9, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM