Q14160 (SCRIB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein scribble homolog
Short name=Scribble
Short name=hScrib

Alternative name(s):
Protein LAP4

Gene names

Name:	SCRIB
Synonyms:	CRIB1, KIAA0147, LAP4, SCRB1, VARTUL

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	1630 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. 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 synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity. Ref.11 Ref.12 Ref.15 Ref.16 Ref.19 Ref.20 Ref.22
Subunit structure	Interacts (via PDZ domains) with VANGL2. Interacts with CTNNB1 and MAPK12 By similarity. Interacts with UBE3A and HPV E6. Interacts with PAK1 and PAK2. Interacts with ARHGEF7 and GIT1; interacts directly with ARHGEF7. Interacts (via PDZ domains) with LPP and TRIP6; the interaction is direct. Interacts (via PDZ domains) with TJP2. Interacts (via PDZ domains) with APC; may mediate APC targeting to adherens junctions of epithelial cells. Interacts (via PDZ domains) with TSHR; regulates TSHR trafficking and function. Interacts with MCC. Interacts (via fourth PDZ domain) with tick-borne encephalitis virus NS5 protein; this interaction inhibits SCRIB and downstream STAT1 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway. Ref.1 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18 Ref.20 Ref.23 Ref.25
Subcellular location	Cell membrane; Peripheral membrane protein. Cell junction › adherens junction. Cytoplasm. Note: Targeting to cell-cell junctions which is CDH1-dependent is required for the pro-apoptotic activity. Localizes to neuronal post- and pre-synaptic regions. Ref.1 Ref.2 Ref.9 Ref.11 Ref.16 Ref.18 Ref.19
Tissue specificity	Expressed in kidney, skeletal muscles, liver, lung, breast, intestine, placenta and skin mainly in epithelial cells (at protein level). Ref.2
Post-translational modification	Ubiquitinated; targeted for UBE3A-dependent multiubiquitination in the presence of high-risk HPV E6 proteins and degraded. Ref.9
Involvement in disease	Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.32
Sequence similarities	Belongs to the LAP (LRR and PDZ) protein family. Contains 16 LRR (leucine-rich) repeats. Contains 4 PDZ (DHR) domains.

Ontologies

Keywords
Biological process	Differentiation Host-virus interaction
Cellular component	Cell junction Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Coiled coil Leucine-rich repeat Repeat
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of Rac GTPase activity Inferred from mutant phenotype Ref.19. Source: UniProtKB apoptotic process involved in morphogenesis Inferred from mutant phenotype Ref.19. Source: UniProtKB asymmetric protein localization Inferred from electronic annotation. Source: Compara cell migration Inferred from mutant phenotype Ref.20. Source: UniProtKB cell proliferation Inferred from direct assay Ref.16. Source: UniProtKB cell-cell adhesion Inferred from genetic interaction Ref.15. Source: UniProtKB establishment of apical/basal cell polarity Inferred from mutant phenotype Ref.19. Source: UniProtKB mammary gland duct morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of mitotic cell cycle Inferred from direct assay Ref.16. Source: UniProtKB neural tube closure Inferred from mutant phenotype Ref.32. Source: UniProtKB positive chemotaxis Inferred from mutant phenotype Ref.20. Source: UniProtKB positive regulation of apoptotic process Inferred from mutant phenotype Ref.19. Source: UniProtKB positive regulation of receptor recycling Inferred from mutant phenotype Ref.12. Source: UniProtKB protein localization to adherens junction Inferred from mutant phenotype Ref.18. Source: BHF-UCL synaptic vesicle endocytosis Inferred from electronic annotation. Source: Compara synaptic vesicle targeting Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	Scrib-APC-beta-catenin complex Inferred from direct assay Ref.18. Source: BHF-UCL basolateral plasma membrane Inferred from electronic annotation. Source: Compara cell-cell adherens junction Inferred from direct assay Ref.16. Source: UniProtKB myelin sheath abaxonal region Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAPK3	P27361	2	EBI-357345,EBI-73995

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14160-1)

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: Q14160-2)

Also known as: Variant N1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q14160-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1565-1565: L → LPLSGKKFDYRAFAALPSSRPVYDIQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1630

1630

Protein scribble homolog

PRO_0000188303

Regions

Repeat

37 – 58

22

LRR 1

Repeat

60 – 81

22

LRR 2

Repeat

83 – 104

22

LRR 3

Repeat

106 – 127

22

LRR 4

Repeat

129 – 150

22

LRR 5

Repeat

152 – 174

23

LRR 6

Repeat

175 – 197

23

LRR 7

Repeat

198 – 219

22

LRR 8

Repeat

221 – 243

23

LRR 9

Repeat

244 – 265

22

LRR 10

Repeat

267 – 288

22

LRR 11

Repeat

290 – 312

23

LRR 12

Repeat

313 – 334

22

LRR 13

Repeat

336 – 357

22

LRR 14

Repeat

359 – 381

23

LRR 15

Repeat

382 – 402

21

LRR 16

Domain

728 – 815

88

PDZ 1

Domain

862 – 950

89

PDZ 2

Domain

1004 – 1093

90

PDZ 3

Domain

1100 – 1194

95

PDZ 4

Region

1 – 818

818

Sufficient for targeting to adherens junction and to inhibit cell proliferation

Region

717 – 1229

513

Interaction with ARHGEF7

Coiled coil

458 – 474

17

Potential

Coiled coil

656 – 701

46

Potential

Coiled coil

1379 – 1419

41

Potential

Compositional bias

660 – 695

36

Glu-rich

Compositional bias

1296 – 1349

54

Pro-rich

Amino acid modifications

Modified residue

688

1

Phosphoserine Ref.30

Modified residue

689

1

Phosphothreonine Ref.30

Modified residue

826

1

Phosphothreonine Ref.24 Ref.27 Ref.28

Modified residue

835

1

Phosphoserine Ref.28

Modified residue

853

1

Phosphoserine Ref.17 Ref.28

Modified residue

939

1

Phosphoserine Ref.24 Ref.28

Modified residue

1140

1

Phosphoserine Ref.28

Modified residue

1220

1

Phosphoserine Ref.10 Ref.27 Ref.28 Ref.30

Modified residue

1223

1

Phosphoserine Ref.24

Modified residue

1232

1

Phosphoserine Ref.24 Ref.28

Modified residue

1306

1

Phosphoserine Ref.17 Ref.24

Modified residue

1309

1

Phosphoserine Ref.17 Ref.24 Ref.30

Modified residue

1342

1

Phosphothreonine Ref.24 Ref.27 Ref.28

Modified residue

1348

1

Phosphoserine Ref.24 Ref.26 Ref.27 Ref.28

Modified residue

1378

1

Phosphoserine Ref.17 Ref.28 Ref.30

Modified residue

1437

1

Phosphoserine Ref.24

Modified residue

1448

1

Phosphoserine Ref.26 Ref.28 Ref.30

Modified residue

1475

1

Phosphoserine Ref.21 Ref.27 Ref.28

Modified residue

1486

1

Phosphoserine Ref.28

Modified residue

1547

1

Phosphoserine Ref.24 Ref.27

Modified residue

1566

1

Phosphoserine Ref.21 Ref.24 Ref.27 Ref.28

Natural variations

Alternative sequence

1 – 81

81

Missing in isoform 2.

VSP_010906

Alternative sequence

1565

1

L → LPLSGKKFDYRAFAALPSSR PVYDIQ in isoform 3.

VSP_010908

Natural variant

422

1

P → L. Ref.1 Ref.2 Ref.3 Ref.4
Corresponds to variant rs6558394 [ dbSNP | Ensembl ].

VAR_019429

Natural variant

454

1

P → S in NTD; protein interactions not affected by the mutation; shows reduced protein localization to the cell membrane. Ref.32

VAR_067219

Natural variant

1535

1

R → Q in NTD; protein interactions not affected by the mutation; shows reduced protein localization to the cell membrane. Ref.32

VAR_067220

Experimental info

Mutagenesis

305

1

P → L: Loss of pro-apoptotic function and of the targeting to cell-cell junctions. Targeted to the cytoplasm. Alters interaction with TJP2. Ref.2 Ref.19

Mutagenesis

738 – 739

2

LG → AE: Alters interaction with LPP.

Mutagenesis

738

1

L → R: Loss of anti-proliferative activity.

Mutagenesis

872 – 873

2

LG → AE: Alters interaction with LPP.

Mutagenesis

1014 – 1015

2

LG → AE: Loss of interaction with LPP and TRIP6. Ref.1

Mutagenesis

1111 – 1112

2

LG → AE: Alters interaction with LPP. Ref.1

Sequence conflict

674

1

V → E in AAP88017. Ref.1

Sequence conflict

674

1

V → E in AAL38976. Ref.2

Sequence conflict

674

1

V → E in AAP88018. Ref.3

Sequence conflict

674

1

V → E in BAA09768. Ref.4

Sequence conflict

1489

1

E → K in AAL38976. Ref.2

Secondary structure

1

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1630

Helix Strand Turn

Details...

Beta strand

726 – 732

7

Beta strand

737 – 744

8

Beta strand

757 – 763

7

Helix

768 – 772

5

Beta strand

779 – 783

5

Helix

793 – 801

9

Beta strand

805 – 812

8

Beta strand

860 – 865

6

Beta strand

875 – 877

3

Beta strand

893 – 896

4

Helix

903 – 906

4

Beta strand

914 – 920

7

Helix

928 – 935

8

Beta strand

942 – 948

7

Beta strand

1097 – 1099

3

Beta strand

1101 – 1104

4

Beta strand

1113 – 1116

4

Beta strand

1119 – 1122

4

Beta strand

1135 – 1139

5

Helix

1144 – 1148

5

Beta strand

1159 – 1162

4

Helix

1170 – 1177

8

Beta strand

1181 – 1186

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 13, 2009. Version 4. Checksum: D71E024FBC4F72D1	FASTA	1,630	174,885
	10 20 30 40 50 60 MLKCIPLWRC NRHVESVDKR HCSLQAVPEE IYRYSRSLEE LLLDANQLRE LPKPFFRLLN 70 80 90 100 110 120 LRKLGLSDNE IQRLPPEVAN FMQLVELDVS RNDIPEIPES IKFCKALEIA DFSGNPLSRL 130 140 150 160 170 180 PDGFTQLRSL AHLALNDVSL QALPGDVGNL ANLVTLELRE NLLKSLPASL SFLVKLEQLD 190 200 210 220 230 240 LGGNDLEVLP DTLGALPNLR ELWLDRNQLS ALPPELGNLR RLVCLDVSEN RLEELPAELG 250 260 270 280 290 300 GLVLLTDLLL SQNLLRRLPD GIGQLKQLSI LKVDQNRLCE VTEAIGDCEN LSELILTENL 310 320 330 340 350 360 LMALPRSLGK LTKLTNLNVD RNHLEALPPE IGGCVALSVL SLRDNRLAVL PPELAHTTEL 370 380 390 400 410 420 HVLDVAGNRL QSLPFALTHL NLKALWLAEN QAQPMLRFQT EDDARTGEKV LTCYLLPQQP 430 440 450 460 470 480 PPSLEDAGQQ GSLSETWSDA PPSRVSVIQF LEAPIGDEDA EEAAAEKRGL QRRATPHPSE 490 500 510 520 530 540 LKVMKRSIEG RRSEACPCQP DSGSPLPAEE EKRLSAESGL SEDSRPSAST VSEAEPEGPS 550 560 570 580 590 600 AEAQGGSQQE ATTAGGEEDA EEDYQEPTVH FAEDALLPGD DREIEEGQPE APWTLPGGRQ 610 620 630 640 650 660 RLIRKDTPHY KKHFKISKLP QPEAVVALLQ GMQPDGEGPV APGGWHNGPH APWAPRAQKE 670 680 690 700 710 720 EEEEEEGSPQ EEEVEEEEEN RAEEEEASTE EEDKEGAVVS APSVKGVSFD QANNLLIEPA 730 740 750 760 770 780 RIEEEELTLT ILRQTGGLGI SIAGGKGSTP YKGDDEGIFI SRVSEEGPAA RAGVRVGDKL 790 800 810 820 830 840 LEVNGVALQG AEHHEAVEAL RGAGTAVQMR VWRERMVEPE NAVTITPLRP EDDYSPRERR 850 860 870 880 890 900 GGGLRLPLLP PESPGPLRQR HVACLARSER GLGFSIAGGK GSTPYRAGDA GIFVSRIAEG 910 920 930 940 950 960 GAAHRAGTLQ VGDRVLSING VDVTEARHDH AVSLLTAASP TIALLLEREA GGPLPPSPLP 970 980 990 1000 1010 1020 HSSPPTAAVA TTSITTATPG VPGLPSLAPS LLAAALEGPY PVEEIRLPRA GGPLGLSIVG 1030 1040 1050 1060 1070 1080 GSDHSSHPFG VQEPGVFISK VLPRGLAARS GLRVGDRILA VNGQDVRDAT HQEAVSALLR 1090 1100 1110 1120 1130 1140 PCLELSLLVR RDPAPPGLRE LCIQKAPGER LGISIRGGAR GHAGNPRDPT DEGIFISKVS 1150 1160 1170 1180 1190 1200 PTGAAGRDGR LRVGLRLLEV NQQSLLGLTH GEAVQLLRSV GDTLTVLVCD GFEASTDAAL 1210 1220 1230 1240 1250 1260 EVSPGVIANP FAAGIGHRNS LESISSIDRE LSPEGPGKEK ELPGQTLHWG PEATEAAGRG 1270 1280 1290 1300 1310 1320 LQPLKLDYRA LAAVPSAGSV QRVPSGAAGG KMAESPCSPS GQQPPSPPSP DELPANVKQA 1330 1340 1350 1360 1370 1380 YRAFAAVPTS HPPEDAPAQP PTPGPAASPE QLSFRERQKY FELEVRVPQA EGPPKRVSLV 1390 1400 1410 1420 1430 1440 GADDLRKMQE EEARKLQQKR AQMLREAAEA GAEARLALDG ETLGEEEQED EQPPWASPSP 1450 1460 1470 1480 1490 1500 TSRQSPASPP PLGGGAPVRT AKAERRHQER LRVQSPEPPA PERALSPAEL RALEAEKRAL 1510 1520 1530 1540 1550 1560 WRAARMKSLE QDALRAQMVL SRSQEGRGTR GPLERLAEAP SPAPTPSPTP VEDLGPQTST 1570 1580 1590 1600 1610 1620 SPGRLSPDFA EELRSLEPSP SPGPQEEDGE VALVLLGRPS PGAVGPEDVA LCSSRRPVRP 1630 GRRGLGPVPS
	Isoform 2 (Variant N1) [UniParc]. Checksum: 88EE83BC4A132CD6	FASTA	1,549	165,243
	10 20 30 40 50 60 MQLVELDVSR NDIPEIPESI KFCKALEIAD FSGNPLSRLP DGFTQLRSLA HLALNDVSLQ 70 80 90 100 110 120 ALPGDVGNLA NLVTLELREN LLKSLPASLS FLVKLEQLDL GGNDLEVLPD TLGALPNLRE 130 140 150 160 170 180 LWLDRNQLSA LPPELGNLRR LVCLDVSENR LEELPAELGG LVLLTDLLLS QNLLRRLPDG 190 200 210 220 230 240 IGQLKQLSIL KVDQNRLCEV TEAIGDCENL SELILTENLL MALPRSLGKL TKLTNLNVDR 250 260 270 280 290 300 NHLEALPPEI GGCVALSVLS LRDNRLAVLP PELAHTTELH VLDVAGNRLQ SLPFALTHLN 310 320 330 340 350 360 LKALWLAENQ AQPMLRFQTE DDARTGEKVL TCYLLPQQPP PSLEDAGQQG SLSETWSDAP 370 380 390 400 410 420 PSRVSVIQFL EAPIGDEDAE EAAAEKRGLQ RRATPHPSEL KVMKRSIEGR RSEACPCQPD 430 440 450 460 470 480 SGSPLPAEEE KRLSAESGLS EDSRPSASTV SEAEPEGPSA EAQGGSQQEA TTAGGEEDAE 490 500 510 520 530 540 EDYQEPTVHF AEDALLPGDD REIEEGQPEA PWTLPGGRQR LIRKDTPHYK KHFKISKLPQ 550 560 570 580 590 600 PEAVVALLQG MQPDGEGPVA PGGWHNGPHA PWAPRAQKEE EEEEEGSPQE EEVEEEEENR 610 620 630 640 650 660 AEEEEASTEE EDKEGAVVSA PSVKGVSFDQ ANNLLIEPAR IEEEELTLTI LRQTGGLGIS 670 680 690 700 710 720 IAGGKGSTPY KGDDEGIFIS RVSEEGPAAR AGVRVGDKLL EVNGVALQGA EHHEAVEALR 730 740 750 760 770 780 GAGTAVQMRV WRERMVEPEN AVTITPLRPE DDYSPRERRG GGLRLPLLPP ESPGPLRQRH 790 800 810 820 830 840 VACLARSERG LGFSIAGGKG STPYRAGDAG IFVSRIAEGG AAHRAGTLQV GDRVLSINGV 850 860 870 880 890 900 DVTEARHDHA VSLLTAASPT IALLLEREAG GPLPPSPLPH SSPPTAAVAT TSITTATPGV 910 920 930 940 950 960 PGLPSLAPSL LAAALEGPYP VEEIRLPRAG GPLGLSIVGG SDHSSHPFGV QEPGVFISKV 970 980 990 1000 1010 1020 LPRGLAARSG LRVGDRILAV NGQDVRDATH QEAVSALLRP CLELSLLVRR DPAPPGLREL 1030 1040 1050 1060 1070 1080 CIQKAPGERL GISIRGGARG HAGNPRDPTD EGIFISKVSP TGAAGRDGRL RVGLRLLEVN 1090 1100 1110 1120 1130 1140 QQSLLGLTHG EAVQLLRSVG DTLTVLVCDG FEASTDAALE VSPGVIANPF AAGIGHRNSL 1150 1160 1170 1180 1190 1200 ESISSIDREL SPEGPGKEKE LPGQTLHWGP EATEAAGRGL QPLKLDYRAL AAVPSAGSVQ 1210 1220 1230 1240 1250 1260 RVPSGAAGGK MAESPCSPSG QQPPSPPSPD ELPANVKQAY RAFAAVPTSH PPEDAPAQPP 1270 1280 1290 1300 1310 1320 TPGPAASPEQ LSFRERQKYF ELEVRVPQAE GPPKRVSLVG ADDLRKMQEE EARKLQQKRA 1330 1340 1350 1360 1370 1380 QMLREAAEAG AEARLALDGE TLGEEEQEDE QPPWASPSPT SRQSPASPPP LGGGAPVRTA 1390 1400 1410 1420 1430 1440 KAERRHQERL RVQSPEPPAP ERALSPAELR ALEAEKRALW RAARMKSLEQ DALRAQMVLS 1450 1460 1470 1480 1490 1500 RSQEGRGTRG PLERLAEAPS PAPTPSPTPV EDLGPQTSTS PGRLSPDFAE ELRSLEPSPS 1510 1520 1530 1540 PGPQEEDGEV ALVLLGRPSP GAVGPEDVAL CSSRRPVRPG RRGLGPVPS
	Isoform 3 [UniParc]. Checksum: BF9BD19ED0A577FA	FASTA	1,655	177,694
	10 20 30 40 50 60 MLKCIPLWRC NRHVESVDKR HCSLQAVPEE IYRYSRSLEE LLLDANQLRE LPKPFFRLLN 70 80 90 100 110 120 LRKLGLSDNE IQRLPPEVAN FMQLVELDVS RNDIPEIPES IKFCKALEIA DFSGNPLSRL 130 140 150 160 170 180 PDGFTQLRSL AHLALNDVSL QALPGDVGNL ANLVTLELRE NLLKSLPASL SFLVKLEQLD 190 200 210 220 230 240 LGGNDLEVLP DTLGALPNLR ELWLDRNQLS ALPPELGNLR RLVCLDVSEN RLEELPAELG 250 260 270 280 290 300 GLVLLTDLLL SQNLLRRLPD GIGQLKQLSI LKVDQNRLCE VTEAIGDCEN LSELILTENL 310 320 330 340 350 360 LMALPRSLGK LTKLTNLNVD RNHLEALPPE IGGCVALSVL SLRDNRLAVL PPELAHTTEL 370 380 390 400 410 420 HVLDVAGNRL QSLPFALTHL NLKALWLAEN QAQPMLRFQT EDDARTGEKV LTCYLLPQQP 430 440 450 460 470 480 PPSLEDAGQQ GSLSETWSDA PPSRVSVIQF LEAPIGDEDA EEAAAEKRGL QRRATPHPSE 490 500 510 520 530 540 LKVMKRSIEG RRSEACPCQP DSGSPLPAEE EKRLSAESGL SEDSRPSAST VSEAEPEGPS 550 560 570 580 590 600 AEAQGGSQQE ATTAGGEEDA EEDYQEPTVH FAEDALLPGD DREIEEGQPE APWTLPGGRQ 610 620 630 640 650 660 RLIRKDTPHY KKHFKISKLP QPEAVVALLQ GMQPDGEGPV APGGWHNGPH APWAPRAQKE 670 680 690 700 710 720 EEEEEEGSPQ EEEVEEEEEN RAEEEEASTE EEDKEGAVVS APSVKGVSFD QANNLLIEPA 730 740 750 760 770 780 RIEEEELTLT ILRQTGGLGI SIAGGKGSTP YKGDDEGIFI SRVSEEGPAA RAGVRVGDKL 790 800 810 820 830 840 LEVNGVALQG AEHHEAVEAL RGAGTAVQMR VWRERMVEPE NAVTITPLRP EDDYSPRERR 850 860 870 880 890 900 GGGLRLPLLP PESPGPLRQR HVACLARSER GLGFSIAGGK GSTPYRAGDA GIFVSRIAEG 910 920 930 940 950 960 GAAHRAGTLQ VGDRVLSING VDVTEARHDH AVSLLTAASP TIALLLEREA GGPLPPSPLP 970 980 990 1000 1010 1020 HSSPPTAAVA TTSITTATPG VPGLPSLAPS LLAAALEGPY PVEEIRLPRA GGPLGLSIVG 1030 1040 1050 1060 1070 1080 GSDHSSHPFG VQEPGVFISK VLPRGLAARS GLRVGDRILA VNGQDVRDAT HQEAVSALLR 1090 1100 1110 1120 1130 1140 PCLELSLLVR RDPAPPGLRE LCIQKAPGER LGISIRGGAR GHAGNPRDPT DEGIFISKVS 1150 1160 1170 1180 1190 1200 PTGAAGRDGR LRVGLRLLEV NQQSLLGLTH GEAVQLLRSV GDTLTVLVCD GFEASTDAAL 1210 1220 1230 1240 1250 1260 EVSPGVIANP FAAGIGHRNS LESISSIDRE LSPEGPGKEK ELPGQTLHWG PEATEAAGRG 1270 1280 1290 1300 1310 1320 LQPLKLDYRA LAAVPSAGSV QRVPSGAAGG KMAESPCSPS GQQPPSPPSP DELPANVKQA 1330 1340 1350 1360 1370 1380 YRAFAAVPTS HPPEDAPAQP PTPGPAASPE QLSFRERQKY FELEVRVPQA EGPPKRVSLV 1390 1400 1410 1420 1430 1440 GADDLRKMQE EEARKLQQKR AQMLREAAEA GAEARLALDG ETLGEEEQED EQPPWASPSP 1450 1460 1470 1480 1490 1500 TSRQSPASPP PLGGGAPVRT AKAERRHQER LRVQSPEPPA PERALSPAEL RALEAEKRAL 1510 1520 1530 1540 1550 1560 WRAARMKSLE QDALRAQMVL SRSQEGRGTR GPLERLAEAP SPAPTPSPTP VEDLGPQTST 1570 1580 1590 1600 1610 1620 SPGRLPLSGK KFDYRAFAAL PSSRPVYDIQ SPDFAEELRS LEPSPSPGPQ EEDGEVALVL 1630 1640 1650 LGRPSPGAVG PEDVALCSSR RPVRPGRRGL GPVPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus." Petit M.M.R., Meulemans S.M.P., Alen P., Ayoubi T.A.Y., Jansen E., Van de Ven W.J.M. BMC Cell Biol. 6:1-1(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH LPP, SUBCELLULAR LOCATION, MUTAGENESIS OF 738-LEU--GLY-739; 872-LEU--GLY-873; 1014-LEU--GLY-1015 AND 1111-LEU--GLY-1112, VARIANT LEU-422.
[2]	"Junctional recruitment of mammalian Scribble relies on E-cadherin engagement." Navarro C., Nola S., Audebert S., Santoni M.-J., Arsanto J.-P., Ginestier C., Marchetto S., Jacquemier J., Isnardon D., Le Bivic A., Birnbaum D., Borg J.-P. Oncogene 24:4330-4339(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-422, SUBCELLULAR LOCATION, MUTAGENESIS OF PRO-305, TISSUE SPECIFICITY.
[3]	"The human Scrib N1 variant encoded by the SCRIB gene contains 13 leucine-rich repeats and 4 PDZ domains." Petit M.M.R., Alen P., Meulemans S.M.P., Van de Wouwer E., Ayoubi T.A.Y., Van de Ven W.J.M., Jansen E. Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-422.
[4]	"Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N. DNA Res. 2:167-174(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-422. Tissue: Bone marrow and Brain.
[5]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[6]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[7]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] OF 799-1630 (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1206-1630 (ISOFORM 3). Tissue: Lung carcinoma and Neuroblastoma.
[9]	"Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase." Nakagawa S., Huibregtse J.M. Mol. Cell. Biol. 20:8244-8253(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE3A AND HPV E6, UBIQUITINATION, SUBCELLULAR LOCATION.
[10]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1220, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Mammalian Scribble forms a tight complex with the betaPIX exchange factor." Audebert S., Navarro C., Nourry C., Chasserot-Golaz S., Lecine P., Bellaiche Y., Dupont J.-L., Premont R.T., Sempere C., Strub J.-M., Van Dorsselaer A., Vitale N., Borg J.-P. Curr. Biol. 14:987-995(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ARHGEF7 AND GIT1, SUBCELLULAR LOCATION.
[12]	"Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway." Lahuna O., Quellari M., Achard C., Nola S., Meduri G., Navarro C., Vitale N., Borg J.-P., Misrahi M. EMBO J. 24:1364-1374(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TSHR.
[13]	"hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells." Metais J.-Y., Navarro C., Santoni M.-J., Audebert S., Borg J.-P. FEBS Lett. 579:3725-3730(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TJP2.
[14]	"The tumor suppressor Scrib selectively interacts with specific members of the zyxin family of proteins." Petit M.M.R., Crombez K.R.M.O., Vervenne H.B.V.K., Weyns N., Van de Ven W.J.M. FEBS Lett. 579:5061-5068(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRIP6.
[15]	"The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin." Qin Y., Capaldo C., Gumbiner B.M., Macara I.G. J. Cell Biol. 171:1061-1071(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL ADHESION.
[16]	"Human homolog of Drosophila tumor suppressor Scribble negatively regulates cell-cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial cells." Nagasaka K., Nakagawa S., Yano T., Takizawa S., Matsumoto Y., Tsuruga T., Nakagawa K., Minaguchi T., Oda K., Hiraike-Wada O., Ooishi H., Yasugi T., Taketani Y. Cancer Sci. 97:1217-1225(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, SUBCELLULAR LOCATION.
[17]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-853; SER-1306; SER-1309 AND SER-1378, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli." Takizawa S., Nagasaka K., Nakagawa S., Yano T., Nakagawa K., Yasugi T., Takeuchi T., Kanda T., Huibregtse J.M., Akiyama T., Taketani Y. Genes Cells 11:453-464(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APC, SUBCELLULAR LOCATION.
[19]	"Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma." Zhan L., Rosenberg A., Bergami K.C., Yu M., Xuan Z., Jaffe A.B., Allred C., Muthuswamy S.K. Cell 135:865-878(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION, MUTAGENESIS OF PRO-305.
[20]	"Scrib regulates PAK activity during the cell migration process." Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S., Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S., Borg J.-P., Santoni M.-J. Hum. Mol. Genet. 17:3552-3565(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL MIGRATION, INTERACTION WITH PAK1 AND PAK2.
[21]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1475 AND SER-1566, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling." Dow L.E., Elsum I.A., King C.L., Kinross K.M., Richardson H.E., Humbert P.O. Oncogene 27:5988-6001(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[23]	"Tick-borne encephalitis virus NS5 associates with membrane protein scribble and impairs interferon-stimulated JAK-STAT signalling." Werme K., Wigerius M., Johansson M. Cell. Microbiol. 10:696-712(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TICK-BORNE ENCEPHALITIS VIRUS RNA-DIRECTED RNA POLYMERASE NS5.
[24]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-826; SER-939; SER-1223; SER-1232; SER-1306; SER-1309; THR-1342; SER-1348; SER-1437; SER-1547 AND SER-1566, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells." Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A., Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P. FEBS Lett. 583:2326-2332(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MCC.
[26]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1348 AND SER-1448, MASS SPECTROMETRY.
[27]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-826; SER-1220; THR-1342; SER-1348; SER-1475; SER-1547 AND SER-1566, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[28]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-826; SER-835; SER-853; SER-939; SER-1140; SER-1220; SER-1232; THR-1342; SER-1348; SER-1378; SER-1448; SER-1475; SER-1486 AND SER-1566, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[29]	"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].
[30]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688; THR-689; SER-1220; SER-1309; SER-1378 AND SER-1448, MASS SPECTROMETRY.
[31]	"Solution structure of the first, second and fourth PDZ domain of human scribble (KIAA0147 protein)." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 718-814; 860-951 AND 1096-1193.
[32]	"Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis." Robinson A., Escuin S., Doudney K., Vekemans M., Stevenson R.E., Greene N.D., Copp A.J., Stanier P. Hum. Mutat. 33:440-447(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NTD SER-454 AND GLN-1535, CHARACTERIZATION OF VARIANTS NTD SER-454 AND GLN-1535.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF240677 mRNA. Translation: AAP88017.1.
AY062238 mRNA. Translation: AAL38976.1.
AF271734 mRNA. Translation: AAP88018.2.
D63481 mRNA. Translation: BAA09768.3.
AC105219 Genomic DNA. No translation available.
BC009490 mRNA. Translation: AAH09490.2.
BC014632 mRNA. Translation: AAH14632.2.

IPI

IPI00410666.
IPI00425560.
IPI00425562.

RefSeq

NP_056171.3. NM_015356.4.
NP_874365.3. NM_182706.4.

UniGene

Hs.436329.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UJU	NMR	-	A	1096-1193	[»]
1WHA	NMR	-	A	860-951	[»]
1X5Q	NMR	-	A	718-814	[»]
2W4F	X-ray	1.30	A	725-815	[»]

ProteinModelPortal

Q14160.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31259N.

IntAct

Q14160. 16 interactions.

MINT

MINT-147371.

STRING

9606.ENSP00000349486.

PTM databases

PhosphoSite

Q14160.

Polymorphism databases

DMDM

261260101.

Proteomic databases

PaxDb

Q14160.

PRIDE

Q14160.

Protocols and materials databases

DNASU

23513.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000320476; ENSP00000322938; ENSG00000180900.
ENST00000356994; ENSP00000349486; ENSG00000180900.
ENST00000377533; ENSP00000366756; ENSG00000180900.
ENST00000564122; ENSP00000456859; ENSG00000260968.
ENST00000567584; ENSP00000456561; ENSG00000260968.
ENST00000569114; ENSP00000455629; ENSG00000260968.

GeneID

23513.

KEGG

hsa:23513.

UCSC

uc003yzo.1. human.
uc003yzp.1. human.

Organism-specific databases

CTD

23513.

GeneCards

GC08M144874.

HGNC

HGNC:30377. SCRIB.

HPA

CAB015463.
CAB022081.
HPA023557.

MIM

182940. phenotype.
607733. gene.

neXtProt

NX_Q14160.

PharmGKB

PA134936275.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4886.

HOGENOM

HOG000113281.

KO

K16175.

OMA

GHRNSLE.

Gene expression databases

ArrayExpress

Q14160.

Bgee

Q14160.

CleanEx

HS_SCRIB.

Genevestigator

Q14160.

GermOnline

ENSG00000180900. Homo sapiens.

Family and domain databases

InterPro

IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR001478. PDZ.
[Graphical view]

Pfam

PF12799. LRR_4. 2 hits.
PF00595. PDZ. 4 hits.
[Graphical view]

SMART

SM00369. LRR_TYP. 2 hits.
SM00228. PDZ. 4 hits.
[Graphical view]

SUPFAM

SSF50156. PDZ. 4 hits.

PROSITE

PS51450. LRR. 13 hits.
PS50106. PDZ. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q14160.

GenomeRNAi

23513.

NextBio

45935.

SOURCE

Search...

Entry information

Entry name

SCRIB_HUMAN

Accession

Primary (citable) accession number: Q14160
Secondary accession number(s): Q6P496 , Q7Z5D1, Q8WWV8, Q96C69, Q96GG1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	October 13, 2009
Last modified:	May 1, 2013
This is version 134 of the entry and version 4 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.