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Protein

Ras GTPase-activating protein 4

Gene

RASA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri675 – 711Btk-typePROSITE-ProRule annotationAdd BLAST37

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • cellular response to calcium ion Source: UniProtKB
  • MAPK cascade Source: Reactome
  • negative regulation of GTPase activity Source: CACAO
  • negative regulation of Ras protein signal transduction Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105808-MONOMER.
ReactomeiR-HSA-5658442. Regulation of RAS by GAPs.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras GTPase-activating protein 4
Alternative name(s):
Calcium-promoted Ras inactivator
Ras p21 protein activator 4
RasGAP-activating-like protein 2
Gene namesi
Name:RASA4
Synonyms:CAPRI, GAPL, KIAA0538
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:23181. RASA4.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication

  • 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.

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • intrinsic component of the cytoplasmic side of the plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10156.
OpenTargetsiENSG00000105808.
PharmGKBiPA134889495.

Polymorphism and mutation databases

BioMutaiRASA4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000566471 – 803Ras GTPase-activating protein 4Add BLAST803

Proteomic databases

EPDiO43374.
MaxQBiO43374.
PaxDbiO43374.
PeptideAtlasiO43374.
PRIDEiO43374.

PTM databases

iPTMnetiO43374.
PhosphoSitePlusiO43374.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000105808.
CleanExiHS_RASA4.
ExpressionAtlasiO43374. baseline and differential.
GenevisibleiO43374. HS.

Organism-specific databases

HPAiHPA043010.

Interactioni

Protein-protein interaction databases

BioGridi115458. 2 interactors.
IntActiO43374. 4 interactors.
MINTiMINT-1370707.
STRINGi9606.ENSP00000262940.

Structurei

3D structure databases

ProteinModelPortaliO43374.
SMRiO43374.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 88C2 1PROSITE-ProRule annotationAdd BLAST88
Domaini129 – 216C2 2PROSITE-ProRule annotationAdd BLAST88
Domaini302 – 512Ras-GAPPROSITE-ProRule annotationAdd BLAST211
Domaini566 – 673PHPROSITE-ProRule annotationAdd BLAST108

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi500 – 503Poly-Leu4

Domaini

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 similaritiesi

Contains 1 Btk-type zinc finger.PROSITE-ProRule annotation
Contains 2 C2 domains.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 Ras-GAP domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri675 – 711Btk-typePROSITE-ProRule annotationAdd BLAST37

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG2059. Eukaryota.
ENOG410Y128. LUCA.
GeneTreeiENSGT00760000119092.
HOGENOMiHOG000234324.
HOVERGENiHBG106587.
InParanoidiO43374.
KOiK17630.
OMAiDLGCDKT.
OrthoDBiEOG091G04T8.
PhylomeDBiO43374.
TreeFamiTF105302.

Family and domain databases

Gene3Di1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 2 hits.
4.10.1130.10. 1 hit.
InterProiIPR000008. C2_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR023152. RasGAP_CS.
IPR001936. RasGAP_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR001562. Znf_Btk_motif.
[Graphical view]
PfamiPF00779. BTK. 1 hit.
PF00168. C2. 2 hits.
PF00169. PH. 1 hit.
PF00616. RasGAP. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00107. BTK. 1 hit.
SM00239. C2. 2 hits.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 2 hits.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50004. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43374-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAKRSSLYIR IVEGKNLPAK DITGSSDPYC IVKVDNEPII RTATVWKTLC
60 70 80 90 100
PFWGEEYQVH LPPTFHAVAF YVMDEDALSR DDVIGKVCLT RDTIASHPKG
110 120 130 140 150
FSGWAHLTEV DPDEEVQGEI HLRLEVWPGA RACRLRCSVL EARDLAPKDR
160 170 180 190 200
NGTSDPFVRV RYKGRTRETS IVKKSCYPRW NETFEFELQE GAMEALCVEA
210 220 230 240 250
WDWDLVSRND FLGKVVIDVQ RLRVVQQEEG WFRLQPDQSK SRRHDEGNLG
260 270 280 290 300
SLQLEVRLRD ETVLPSSYYQ PLVHLLCHEV KLGMQGPGQL IPLIEETTST
310 320 330 340 350
ECRQDVATNL LKLFLGQGLA KDFLDLLFQL ELSRTSETNT LFRSNSLASK
360 370 380 390 400
SMESFLKVAG MQYLHGVLGP IINKVFEEKK YVELDPSKVE VKDVGCSGLH
410 420 430 440 450
RPQTEAEVLE QSAQTLRAHL GALLSALSRS VRACPAVVRA TFRQLFRRVR
460 470 480 490 500
ERFPGAQHEN VPFIAVTSFL CLRFFSPAIM SPKLFHLRER HADARTSRTL
510 520 530 540 550
LLLAKAVQNV GNMDTPASRA KEAWMEPLQP TVRQGVAQLK DFITKLVDIE
560 570 580 590 600
EKDELDLQRT LSLQAPPVKE GPLFIHRTKG KGPLMSSSFK KLYFSLTTEA
610 620 630 640 650
LSFAKTPSSK KSALIKLANI RAAEKVEEKS FGGSHVMQVI YTDDAGRPQT
660 670 680 690 700
AYLQCKCVNE LNQWLSALRK VSINNTGLLG SYHPGVFRGD KWSCCHQKEK
710 720 730 740 750
TGQGCDKTRS RVTLQEWNDP LDHDLEAQLI YRHLLGVEAM LWERHRELSG
760 770 780 790 800
GAEAGTVPTS PGKVPEDSLA RLLRVLQDLR EAHSSSPAGS PPSEPNCLLE

LQT
Length:803
Mass (Da):90,458
Last modified:August 15, 2003 - v2
Checksum:i6E70DBF2F8F5D0E9
GO
Isoform 2 (identifier: O43374-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     611-656: Missing.

Note: No experimental confirmation available.
Show »
Length:757
Mass (Da):85,409
Checksum:iEEBA12E7214670AB
GO

Sequence cautioni

The sequence AAB97935 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAP22345 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAA25464 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213G → V in AK026441 (PubMed:14702039).Curated1
Sequence conflicti260D → G in AK026441 (PubMed:14702039).Curated1
Sequence conflicti429R → L in AK026441 (PubMed:14702039).Curated1
Sequence conflicti480M → V in AK026441 (PubMed:14702039).Curated1
Sequence conflicti606T → M in BAA25464 (PubMed:9628581).Curated1
Sequence conflicti752A → T in BAA25464 (PubMed:9628581).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027680352M → V.2 PublicationsCorresponds to variant rs746316dbSNPEnsembl.1
Natural variantiVAR_027681432R → P.Corresponds to variant rs886346dbSNPEnsembl.1
Natural variantiVAR_027682731Y → C.Corresponds to variant rs1060228dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039965611 – 656Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47674.1. [O43374-2]
CCDS5725.1. [O43374-1]
RefSeqiNP_001073346.2. NM_001079877.2. [O43374-2]
NP_008920.5. NM_006989.5. [O43374-1]
UniGeneiHs.530089.
Hs.656696.

Genome annotation databases

EnsembliENST00000262940; ENSP00000262940; ENSG00000105808. [O43374-1]
ENST00000449970; ENSP00000412876; ENSG00000105808. [O43374-2]
GeneIDi10156.
KEGGihsa:10156.
UCSCiuc003vae.4. human. [O43374-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47674.1. [O43374-2]
CCDS5725.1. [O43374-1]
RefSeqiNP_001073346.2. NM_001079877.2. [O43374-2]
NP_008920.5. NM_006989.5. [O43374-1]
UniGeneiHs.530089.
Hs.656696.

3D structure databases

ProteinModelPortaliO43374.
SMRiO43374.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115458. 2 interactors.
IntActiO43374. 4 interactors.
MINTiMINT-1370707.
STRINGi9606.ENSP00000262940.

PTM databases

iPTMnetiO43374.
PhosphoSitePlusiO43374.

Polymorphism and mutation databases

BioMutaiRASA4.

Proteomic databases

EPDiO43374.
MaxQBiO43374.
PaxDbiO43374.
PeptideAtlasiO43374.
PRIDEiO43374.

Protocols and materials databases

DNASUi10156.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262940; ENSP00000262940; ENSG00000105808. [O43374-1]
ENST00000449970; ENSP00000412876; ENSG00000105808. [O43374-2]
GeneIDi10156.
KEGGihsa:10156.
UCSCiuc003vae.4. human. [O43374-1]

Organism-specific databases

CTDi10156.
DisGeNETi10156.
GeneCardsiRASA4.
H-InvDBHIX0034020.
HIX0201129.
HGNCiHGNC:23181. RASA4.
HPAiHPA043010.
MIMi607943. gene.
neXtProtiNX_O43374.
OpenTargetsiENSG00000105808.
PharmGKBiPA134889495.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2059. Eukaryota.
ENOG410Y128. LUCA.
GeneTreeiENSGT00760000119092.
HOGENOMiHOG000234324.
HOVERGENiHBG106587.
InParanoidiO43374.
KOiK17630.
OMAiDLGCDKT.
OrthoDBiEOG091G04T8.
PhylomeDBiO43374.
TreeFamiTF105302.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105808-MONOMER.
ReactomeiR-HSA-5658442. Regulation of RAS by GAPs.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.

Miscellaneous databases

ChiTaRSiRASA4. human.
GeneWikiiRASA4.
GenomeRNAii10156.
PROiO43374.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105808.
CleanExiHS_RASA4.
ExpressionAtlasiO43374. baseline and differential.
GenevisibleiO43374. HS.

Family and domain databases

Gene3Di1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 2 hits.
4.10.1130.10. 1 hit.
InterProiIPR000008. C2_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR023152. RasGAP_CS.
IPR001936. RasGAP_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR001562. Znf_Btk_motif.
[Graphical view]
PfamiPF00779. BTK. 1 hit.
PF00168. C2. 2 hits.
PF00169. PH. 1 hit.
PF00616. RasGAP. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00107. BTK. 1 hit.
SM00239. C2. 2 hits.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 2 hits.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50004. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiRASL2_HUMAN
AccessioniPrimary (citable) accession number: O43374
Secondary accession number(s): O60286
, Q14CQ4, Q86UW3, Q96QU0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: August 15, 2003
Last modified: November 30, 2016
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.