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Protein

Sterol regulatory element-binding protein cleavage-activating protein

Gene

SCAP

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

Functioni

Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SREBF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the transcription factor fragment of SREBF from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity).By similarity

GO - Molecular functioni

  • cholesterol binding Source: InterPro
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • aging Source: Ensembl
  • cholesterol metabolic process Source: UniProtKB-KW
  • negative regulation of cholesterol biosynthetic process Source: UniProtKB
  • positive regulation of low-density lipoprotein particle receptor biosynthetic process Source: UniProtKB
  • regulation of fatty acid biosynthetic process Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to insulin Source: Ensembl
  • SREBP signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

ReactomeiR-HSA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
SignaLinkiQ12770.

Names & Taxonomyi

Protein namesi
Recommended name:
Sterol regulatory element-binding protein cleavage-activating protein
Short name:
SCAP
Short name:
SREBP cleavage-activating protein
Gene namesi
Name:SCAP
Synonyms:KIAA0199
ORF Names:PSEC0227
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:30634. SCAP.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1818CytoplasmicBy similarityAdd
BLAST
Transmembranei19 – 3921Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini40 – 279240LumenalBy similarityAdd
BLAST
Transmembranei280 – 30021Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini301 – 31212CytoplasmicBy similarityAdd
BLAST
Transmembranei313 – 33321Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini334 – 34411LumenalBy similarityAdd
BLAST
Transmembranei345 – 36521Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini366 – 40136CytoplasmicBy similarityAdd
BLAST
Transmembranei402 – 42221Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini423 – 4231LumenalBy similarity
Transmembranei424 – 44421Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini445 – 51874CytoplasmicBy similarityAdd
BLAST
Transmembranei519 – 53921Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini540 – 709170LumenalBy similarityAdd
BLAST
Transmembranei710 – 73021Helical; Name=8Sequence analysisAdd
BLAST
Topological domaini731 – 1279549CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • ER to Golgi transport vesicle membrane Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: Reactome
  • integral component of membrane Source: UniProtKB
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162402461.

Polymorphism and mutation databases

BioMutaiSCAP.
DMDMi116242783.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12791279Sterol regulatory element-binding protein cleavage-activating proteinPRO_0000051208Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi263 – 2631N-linked (GlcNAc...)Sequence analysis
Glycosylationi590 – 5901N-linked (GlcNAc...)Sequence analysis
Glycosylationi641 – 6411N-linked (GlcNAc...)Sequence analysis
Modified residuei822 – 8221PhosphoserineCombined sources
Modified residuei838 – 8381PhosphoserineCombined sources
Modified residuei851 – 8511PhosphoserineCombined sources
Modified residuei907 – 9071PhosphoserineCombined sources
Modified residuei937 – 9371PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ12770.
MaxQBiQ12770.
PaxDbiQ12770.
PeptideAtlasiQ12770.
PRIDEiQ12770.
TopDownProteomicsiQ12770-2. [Q12770-2]

PTM databases

iPTMnetiQ12770.
PhosphoSiteiQ12770.

Expressioni

Inductioni

By androgen-bound AR and glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP).1 Publication

Gene expression databases

BgeeiENSG00000114650.
CleanExiHS_SCAP.
ExpressionAtlasiQ12770. baseline and differential.
GenevisibleiQ12770. HS.

Organism-specific databases

HPAiHPA004713.

Interactioni

Subunit structurei

Membrane region forms a homotetramer. Forms a stable complex with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal cytoplasmic domain. Forms a ternary complex with INSIG1 or INSIG2 through its transmembrane domains at high sterol concentrations. Interacts with the SEC23/SEC24 complex in a SAR1-GTP-dependent manner through an ER export signal in its third cytoplasmic loop. Binds cholesterol through its SSC domain (By similarity). Component of SCAP/SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts with RNF139; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP/SREBP complex.By similarity1 Publication

GO - Molecular functioni

  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116596. 20 interactions.
IntActiQ12770. 2 interactions.
STRINGi9606.ENSP00000265565.

Structurei

3D structure databases

ProteinModelPortaliQ12770.
SMRiQ12770. Positions 771-803, 968-1271.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini284 – 442159SSDPROSITE-ProRule annotationAdd
BLAST
Repeati771 – 81141WD 1Add
BLAST
Repeati952 – 100251WD 2Add
BLAST
Repeati1005 – 104238WD 3Add
BLAST
Repeati1077 – 111438WD 4Add
BLAST
Repeati1117 – 115539WD 5Add
BLAST
Repeati1158 – 119538WD 6Add
BLAST
Repeati1197 – 123539WD 7Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni447 – 4526ER export signalBy similarity
Regioni731 – 1279549Interaction with SREBF2By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi722 – 7298Poly-Leu
Compositional biasi747 – 7504Poly-Arg
Compositional biasi861 – 8644Poly-Pro

Domaini

Cholesterol bound to SSC domain of SCAP or oxysterol bound to INSIG1/2 leads to masking of an ER export signal on SCAP possibly by moving the signal further away from the ER membrane.By similarity

Sequence similaritiesi

Belongs to the WD repeat SCAP family.Curated
Contains 1 SSD (sterol-sensing) domain.PROSITE-ProRule annotation
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix, WD repeat

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
GeneTreeiENSGT00840000129955.
HOGENOMiHOG000230538.
HOVERGENiHBG019538.
InParanoidiQ12770.
OMAiNSEAQPA.
OrthoDBiEOG091G04AA.
PhylomeDBiQ12770.
TreeFamiTF315236.

Family and domain databases

Gene3Di2.130.10.10. 3 hits.
InterProiIPR030225. SCAP.
IPR000731. SSD.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR10796:SF127. PTHR10796:SF127. 2 hits.
PfamiPF12349. Sterol-sensing. 1 hit.
PF00400. WD40. 1 hit.
[Graphical view]
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 3 hits.
PROSITEiPS50156. SSD. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q12770-1) [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
MTLTERLREK ISRAFYNHGL LCASYPIPII LFTGFCILAC CYPLLKLPLP
60 70 80 90 100
GTGPVEFTTP VKDYSPPPVD SDRKQGEPTE QPEWYVGAPV AYVQQIFVKS
110 120 130 140 150
SVFPWHKNLL AVDVFRSPLS RAFQLVEEIR NHVLRDSSGI RSLEELCLQV
160 170 180 190 200
TDLLPGLRKL RNLLPEHGCL LLSPGNFWQN DWERFHADPD IIGTIHQHEP
210 220 230 240 250
KTLQTSATLK DLLFGVPGKY SGVSLYTRKR MVSYTITLVF QHYHAKFLGS
260 270 280 290 300
LRARLMLLHP SPNCSLRAES LVHVHFKEEI GVAELIPLVT TYIILFAYIY
310 320 330 340 350
FSTRKIDMVK SKWGLALAAV VTVLSSLLMS VGLCTLFGLT PTLNGGEIFP
360 370 380 390 400
YLVVVIGLEN VLVLTKSVVS TPVDLEVKLR IAQGLSSESW SIMKNMATEL
410 420 430 440 450
GIILIGYFTL VPAIQEFCLF AVVGLVSDFF LQMLFFTTVL SIDIRRMELA
460 470 480 490 500
DLNKRLPPEA CLPSAKPVGQ PTRYERQLAV RPSTPHTITL QPSSFRNLRL
510 520 530 540 550
PKRLRVVYFL ARTRLAQRLI MAGTVVWIGI LVYTDPAGLR NYLAAQVTEQ
560 570 580 590 600
SPLGEGALAP MPVPSGMLPP SHPDPAFSIF PPDAPKLPEN QTSPGESPER
610 620 630 640 650
GGPAEVVHDS PVPEVTWGPE DEELWRKLSF RHWPTLFSYY NITLAKRYIS
660 670 680 690 700
LLPVIPVTLR LNPREALEGR HPQDGRSAWP PPGPIPAGHW EAGPKGPGGV
710 720 730 740 750
QAHGDVTLYK VAALGLATGI VLVLLLLCLY RVLCPRNYGQ LGGGPGRRRR
760 770 780 790 800
GELPCDDYGY APPETEIVPL VLRGHLMDIE CLASDGMLLV SCCLAGHVCV
810 820 830 840 850
WDAQTGDCLT RIPRPGRQRR DSGVGSGLEA QESWERLSDG GKAGPEEPGD
860 870 880 890 900
SPPLRHRPRG PPPPSLFGDQ PDLTCLIDTN FSAQPRSSQP TQPEPRHRAV
910 920 930 940 950
CGRSRDSPGY DFSCLVQRVY QEEGLAAVCT PALRPPSPGP VLSQAPEDEG
960 970 980 990 1000
GSPEKGSPSL AWAPSAEGSI WSLELQGNLI VVGRSSGRLE VWDAIEGVLC
1010 1020 1030 1040 1050
CSSEEVSSGI TALVFLDKRI VAARLNGSLD FFSLETHTAL SPLQFRGTPG
1060 1070 1080 1090 1100
RGSSPASPVY SSSDTVACHL THTVPCAHQK PITALKAAAG RLVTGSQDHT
1110 1120 1130 1140 1150
LRVFRLEDSC CLFTLQGHSG AITTVYIDQT MVLASGGQDG AICLWDVLTG
1160 1170 1180 1190 1200
SRVSHVFAHR GDVTSLTCTT SCVISSGLDD LISIWDRSTG IKFYSIQQDL
1210 1220 1230 1240 1250
GCGASLGVIS DNLLVTGGQG CVSFWDLNYG DLLQTVYLGK NSEAQPARQI
1260 1270
LVLDNAAIVC NFGSELSLVY VPSVLEKLD
Length:1,279
Mass (Da):139,729
Last modified:October 17, 2006 - v4
Checksum:i4CD73543B7D2ACB4
GO
Isoform 2 (identifier: Q12770-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     29-401: Missing.
     817-817: Missing.

Note: No experimental confirmation available.
Show »
Length:905
Mass (Da):97,903
Checksum:i7998FC1DB49E4CDC
GO
Isoform 3 (identifier: Q12770-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     476-983: Missing.

Note: No experimental confirmation available.
Show »
Length:771
Mass (Da):84,773
Checksum:iDE4C276926DBA281
GO
Isoform 4 (identifier: Q12770-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-392: Missing.
     817-817: Missing.

Note: No experimental confirmation available.
Show »
Length:886
Mass (Da):95,616
Checksum:i5ED9E0586FA01C37
GO

Sequence cautioni

The sequence BAA12111 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAC11673 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti350 – 3501P → G in BAC11673 (PubMed:16303743).Curated
Sequence conflicti427 – 4271S → T in BAC11673 (PubMed:16303743).Curated
Sequence conflicti617 – 6171W → R in BAB55088 (PubMed:14702039).Curated
Sequence conflicti753 – 7531L → Q in BAB55088 (PubMed:14702039).Curated
Sequence conflicti941 – 9411V → A in BAB55088 (PubMed:14702039).Curated
Sequence conflicti994 – 9941A → S in BAC11673 (PubMed:16303743).Curated
Sequence conflicti1019 – 10191R → G in BAC11673 (PubMed:16303743).Curated
Sequence conflicti1035 – 10351E → G in BAB55088 (PubMed:14702039).Curated
Sequence conflicti1080 – 10801K → E in BAB55088 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti798 – 7981V → I.1 Publication
Corresponds to variant rs12487736 [ dbSNP | Ensembl ].
VAR_012203

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 392392Missing in isoform 4. 1 PublicationVSP_021105Add
BLAST
Alternative sequencei29 – 401373Missing in isoform 2. 1 PublicationVSP_007451Add
BLAST
Alternative sequencei476 – 983508Missing in isoform 3. 1 PublicationVSP_007452Add
BLAST
Alternative sequencei817 – 8171Missing in isoform 2 and isoform 4. 2 PublicationsVSP_021106

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D83782 mRNA. Translation: BAA12111.2. Different initiation.
AK027402 mRNA. Translation: BAB55088.1.
BC020987 mRNA. Translation: AAH20987.1.
AK075528 mRNA. Translation: BAC11673.1. Different initiation.
CCDSiCCDS2755.2. [Q12770-1]
RefSeqiNP_036367.2. NM_012235.3. [Q12770-1]
XP_011531803.1. XM_011533501.1. [Q12770-1]
UniGeneiHs.531789.

Genome annotation databases

EnsembliENST00000265565; ENSP00000265565; ENSG00000114650. [Q12770-1]
GeneIDi22937.
KEGGihsa:22937.
UCSCiuc003crh.2. human. [Q12770-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D83782 mRNA. Translation: BAA12111.2. Different initiation.
AK027402 mRNA. Translation: BAB55088.1.
BC020987 mRNA. Translation: AAH20987.1.
AK075528 mRNA. Translation: BAC11673.1. Different initiation.
CCDSiCCDS2755.2. [Q12770-1]
RefSeqiNP_036367.2. NM_012235.3. [Q12770-1]
XP_011531803.1. XM_011533501.1. [Q12770-1]
UniGeneiHs.531789.

3D structure databases

ProteinModelPortaliQ12770.
SMRiQ12770. Positions 771-803, 968-1271.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116596. 20 interactions.
IntActiQ12770. 2 interactions.
STRINGi9606.ENSP00000265565.

PTM databases

iPTMnetiQ12770.
PhosphoSiteiQ12770.

Polymorphism and mutation databases

BioMutaiSCAP.
DMDMi116242783.

Proteomic databases

EPDiQ12770.
MaxQBiQ12770.
PaxDbiQ12770.
PeptideAtlasiQ12770.
PRIDEiQ12770.
TopDownProteomicsiQ12770-2. [Q12770-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265565; ENSP00000265565; ENSG00000114650. [Q12770-1]
GeneIDi22937.
KEGGihsa:22937.
UCSCiuc003crh.2. human. [Q12770-1]

Organism-specific databases

CTDi22937.
GeneCardsiSCAP.
H-InvDBHIX0031165.
HGNCiHGNC:30634. SCAP.
HPAiHPA004713.
MIMi601510. gene.
neXtProtiNX_Q12770.
PharmGKBiPA162402461.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
GeneTreeiENSGT00840000129955.
HOGENOMiHOG000230538.
HOVERGENiHBG019538.
InParanoidiQ12770.
OMAiNSEAQPA.
OrthoDBiEOG091G04AA.
PhylomeDBiQ12770.
TreeFamiTF315236.

Enzyme and pathway databases

ReactomeiR-HSA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
SignaLinkiQ12770.

Miscellaneous databases

ChiTaRSiSCAP. human.
GeneWikiiSREBP_cleavage_activating_protein.
GenomeRNAii22937.
PROiQ12770.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114650.
CleanExiHS_SCAP.
ExpressionAtlasiQ12770. baseline and differential.
GenevisibleiQ12770. HS.

Family and domain databases

Gene3Di2.130.10.10. 3 hits.
InterProiIPR030225. SCAP.
IPR000731. SSD.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR10796:SF127. PTHR10796:SF127. 2 hits.
PfamiPF12349. Sterol-sensing. 1 hit.
PF00400. WD40. 1 hit.
[Graphical view]
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 3 hits.
PROSITEiPS50156. SSD. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSCAP_HUMAN
AccessioniPrimary (citable) accession number: Q12770
Secondary accession number(s): Q8N2E0, Q8WUA1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: October 17, 2006
Last modified: September 7, 2016
This is version 161 of the entry and version 4 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 3
    Human chromosome 3: 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.