Protein: Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) (Q14160)
Organism: Homo sapiens (Human)
Function: Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization. Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Most probably functions in the establishment of apico-basal cell polarity. May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium. May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling. May play a role in exocytosis and in the targeting of synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity.
Subcellular location: Cell membrane {ECO:0000269|PubMed:19386766, ECO:0000269|PubMed:21849460, ECO:0000269|PubMed:28169360}; Peripheral membrane protein. Cell junction {ECO:0000269|PubMed:27380321}. Cell junction, adherens junction. Cell projection, lamellipodium. Cytoplasm {ECO:0000269|PubMed:19386766}. Postsynapse {ECO:0000269|PubMed:15182672}. Presynapse {ECO:0000269|PubMed:15182672}. Note=Targeting to cell-cell junctions which is CDH1-dependent is required for the pro-apoptotic activity. In a subset of CD4+ T-cells, colocalizes with CRTAM at the immunological synapse during the late phase of T-cell activation (By similarity). Localized to small puncta throughout the cytoplasm and cell membrane when in the presence of SNAIL1 (By similarity). Localized along the length of perinuclear emanating vimentin bundles and at vimentin-positive fibrils at the cell periphery (PubMed:19386766). Localized to the lateral plasma membrane during the establishment and maturation of cell-cell contacts (PubMed:19386766). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:19386766}.
Sequence: MLKCIPLWRCNRHVESVDKRHCSLQAVPEEIYRYSRSLEELLLDANQLRELPKPFFRLLNLRKLGLSDNEIQRLPPEVANFMQLVELDVSRNDIPEIPESIKFCKALEIADFSGNPLSRLPDGFTQLRSLAHLALNDVSLQALPGDVGNLANLVTLELRENLLKSLPASLSFLVKLEQLDLGGNDLEVLPDTLGALPNLRELWLDRNQLSALPPELGNLRRLVCLDVSENRLEELPAELGGLVLLTDLLLSQNLLRRLPDGIGQLKQLSILKVDQNRLCEVTEAIGDCENLSELILTENLLMALPRSLGKLTKLTNLNVDRNHLEALPPEIGGCVALSVLSLRDNRLAVLPPELAHTTELHVLDVAGNRLQSLPFALTHLNLKALWLAENQAQPMLRFQTEDDARTGEKVLTCYLLPQQPPPSLEDAGQQGSLSETWSDAPPSRVSVIQFLEAPIGDEDAEEAAAEKRGLQRRATPHPSELKVMKRSIEGRRSEACPCQPDSGSPLPAEEEKRLSAESGLSEDSRPSASTVSEAEPEGPSAEAQGGSQQEATTAGGEEDAEEDYQEPTVHFAEDALLPGDDREIEEGQPEAPWTLPGGRQRLIRKDTPHYKKHFKISKLPQPEAVVALLQGMQPDGEGPVAPGGWHNGPHAPWAPRAQKEEEEEEEGSPQEEEEEEEEENRAEEEEASTEEEDKEGAVVSAPSVKGVSFDQANNLLIEPARIEEEELTLTILRQTGGLGISIAGGKGSTPYKGDDEGIFISRVSEEGPAARAGVRVGDKLLEVNGVALQGAEHHEAVEALRGAGTAVQMRVWRERMVEPENAVTITPLRPEDDYSPRERRGGGLRLPLLPPESPGPLRQRHVACLARSERGLGFSIAGGKGSTPYRAGDAGIFVSRIAEGGAAHRAGTLQVGDRVLSINGVDVTEARHDHAVSLLTAASPTIALLLEREAGGPLPPSPLPHSSPPTAAVATTSITTATPGVPGLPSLAPSLLAAALEGPYPVEEIRLPRAGGPLGLSIVGGSDHSSHPFGVQEPGVFISKVLPRGLAARSGLRVGDRILAVNGQDVRDATHQEAVSALLRPCLELSLLVRRDPAPPGLRELCIQKAPGERLGISIRGGARGHAGNPRDPTDEGIFISKVSPTGAAGRDGRLRVGLRLLEVNQQSLLGLTHGEAVQLLRSVGDTLTVLVCDGFEASTDAALEVSPGVIANPFAAGIGHRNSLESISSIDRELSPEGPGKEKELPGQTLHWGPEATEAAGRGLQPLKLDYRALAAVPSAGSVQRVPSGAAGGKMAESPCSPSGQQPPSPPSPDELPANVKQAYRAFAAVPTSHPPEDAPAQPPTPGPAASPEQLSFRERQKYFELEVRVPQAEGPPKRVSLVGADDLRKMQEEEARKLQQKRAQMLREAAEAGAEARLALDGETLGEEEQEDEQPPWASPSPTSRQSPASPPPLGGGAPVRTAKAERRHQERLRVQSPEPPAPERALSPAELRALEAEKRALWRAARMKSLEQDALRAQMVLSRSQEGRGTRGPLERLAEAPSPAPTPSPTPVEDLGPQTSTSPGRLPLSGKKFDYRAFAALPSSRPVYDIQSPDFAEELRSLEPSPSPGPQEEDGEVALVLLGRPSPGAVGPEDVALCSSRRPVRPGRRGLGPVPS
InterPro domains: - IPR036034: PDZ superfamily (homologous_superfamily) [719-1203]
- IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [6-399]
- IPR055414: Disease resistance R13L4/SHOC-2-like, LRR domain (domain) [192-323]
- IPR003591: Leucine-rich repeat, typical subtype (repeat) [58-380]
- IPR050614: Synaptic Scaffolding LAP/MAGUK Families (family) [1-1412]
- IPR001611: Leucine-rich repeat (repeat) [36-219]
- IPR001478: PDZ domain (domain) [728-1192]
Interaction partners: - Rho guanine nucleotide exchange factor 7
- Vang-like protein 2
- ARF GTPase-activating protein GIT1
- Ubiquitin-protein ligase E3A
- Lethal
- LLGL scribble cell polarity complex component 2
- Vang-like protein 1
- Tight junction protein 2
- Disks large homolog 4
- Disks large homolog 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0065008 (regulation of biological quality), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0031503 (protein-containing complex localization), GO:0048870 (cell motility), GO:0032879 (regulation of localization), GO:0050794 (regulation of cellular process), GO:0051234 (establishment of localization), GO:0033036 (macromolecule localization), GO:0099149 (regulation of postsynaptic neurotransmitter receptor internalization), GO:0051049 (regulation of transport), GO:0099637 (neurotransmitter receptor transport), GO:0046907 (intracellular transport), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0006810 (transport), GO:0070727 (cellular macromolecule localization), GO:0051649 (establishment of localization in cell), GO:0060627 (regulation of vesicle-mediated transport), GO:0099072 (regulation of postsynaptic membrane neurotransmitter receptor levels), GO:0051128 (regulation of cellular component organization), GO:0051668 (localization within membrane), GO:0045184 (establishment of protein localization), GO:0097120 (receptor localization to synapse), GO:0016477 (cell migration), GO:0030100 (regulation of endocytosis), GO:0022008 (neurogenesis), GO:0098969 (neurotransmitter receptor transport to postsynaptic membrane), GO:0006886 (intracellular protein transport), GO:0071705 (nitrogen compound transport), GO:0016197 (endosomal transport), GO:0007399 (nervous system development), GO:0098876 (vesicle-mediated transport to the plasma membrane), GO:0015031 (protein transport), GO:0008347 (glial cell migration), GO:0071702 (organic substance transport), GO:0016192 (vesicle-mediated transport), GO:0008104 (protein localization), GO:0098877 (neurotransmitter receptor transport to plasma membrane), GO:0090150 (establishment of protein localization to membrane), GO:0072657 (protein localization to membrane), GO:0048259 (regulation of receptor-mediated endocytosis), GO:0099638 (endosome to plasma membrane protein transport), GO:1902414 (protein localization to cell junction), GO:0042063 (gliogenesis), GO:0099003 (vesicle-mediated transport in synapse), GO:0072659 (protein localization to plasma membrane), GO:0032456 (endocytic recycling), GO:1903539 (protein localization to postsynaptic membrane), GO:1990778 (protein localization to cell periphery), GO:1903540 (establishment of protein localization to postsynaptic membrane), GO:0061951 (establishment of protein localization to plasma membrane), GO:0035418 (protein localization to synapse), GO:0002090 (regulation of receptor internalization), GO:0062237 (protein localization to postsynapse)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0030054 (cell junction), GO:0071944 (cell periphery), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)