RASA4

Protein identityUniProt · HPA

UniProt accession

O43374

Gene

RASA4

Ensembl

ENSG00000105808

Chromosome

7

Canonical length

803 aa

Protein class

Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Vesicles,Cell Junctions

OverviewNCBI Gene

This gene encodes a member of the GAP1 family of GTPase-activating proteins that suppresses the Ras/mitogen-activated protein kinase pathway in response to Ca(2+). Stimuli that increase intracellular Ca(2+) levels result in the translocation of this protein to the plasma membrane, where it activates Ras GTPase activity. Consequently, Ras is converted from the active GTP-bound state to the inactive GDP-bound state and no longer activates downstream pathways that regulate gene expression, cell growth, and differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

803 residues, UniProt reviewed canonical sequence.

>O43374|RASA4
     1  MAKRSSLYIR IVEGKNLPAK DITGSSDPYC IVKVDNEPII RTATVWKTLC PFWGEEYQVH
    61  LPPTFHAVAF YVMDEDALSR DDVIGKVCLT RDTIASHPKG FSGWAHLTEV DPDEEVQGEI
   121  HLRLEVWPGA RACRLRCSVL EARDLAPKDR NGTSDPFVRV RYKGRTRETS IVKKSCYPRW
   181  NETFEFELQE GAMEALCVEA WDWDLVSRND FLGKVVIDVQ RLRVVQQEEG WFRLQPDQSK
   241  SRRHDEGNLG SLQLEVRLRD ETVLPSSYYQ PLVHLLCHEV KLGMQGPGQL IPLIEETTST
   301  ECRQDVATNL LKLFLGQGLA KDFLDLLFQL ELSRTSETNT LFRSNSLASK SMESFLKVAG
   361  MQYLHGVLGP IINKVFEEKK YVELDPSKVE VKDVGCSGLH RPQTEAEVLE QSAQTLRAHL
   421  GALLSALSRS VRACPAVVRA TFRQLFRRVR ERFPGAQHEN VPFIAVTSFL CLRFFSPAIM
   481  SPKLFHLRER HADARTSRTL LLLAKAVQNV GNMDTPASRA KEAWMEPLQP TVRQGVAQLK
   541  DFITKLVDIE EKDELDLQRT LSLQAPPVKE GPLFIHRTKG KGPLMSSSFK KLYFSLTTEA
   601  LSFAKTPSSK KSALIKLANI RAAEKVEEKS FGGSHVMQVI YTDDAGRPQT AYLQCKCVNE
   661  LNQWLSALRK VSINNTGLLG SYHPGVFRGD KWSCCHQKEK TGQGCDKTRS RVTLQEWNDP
   721  LDHDLEAQLI YRHLLGVEAM LWERHRELSG GAEAGTVPTS PGKVPEDSLA RLLRVLQDLR
   781  EAHSSSPAGS PPSEPNCLLE LQT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RASA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

223 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.2

gnomAD pLI

0.12

gnomAD missense Z

0.84

DepMap mean gene effect

-0.41

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to calcium ion
• intracellular signal transduction
• negative regulation of GTPase activity
• negative regulation of Ras protein signal transduction
• regulation of intracellular signal transduction

Molecular functions

• GTPase activator activity
• phospholipid binding
• zinc ion binding

Cellular components

• cytosol
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• C2 domain
• Zinc finger, Btk motif
• Pleckstrin homology domain
• Ras GTPase-activating domain
• Rho GTPase activation protein
• PH-like domain superfamily
• Ras GTPase-activating protein, conserved site
• C2 domain superfamily
• RASA4, PH domain
• Ras GTPase-activating protein
• C2 domain
• PH domain
• GTPase-activator protein for Ras-like GTPase
• BTK motif

KeywordsUniProt

• Calcium
• Cell membrane
• Cytoplasm
• GTPase activation
• Membrane
• Metal-binding
• Repeat
• Zinc
• Zinc-finger