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Q9NRQ2

- PLS4_HUMAN

UniProt

Q9NRQ2 - PLS4_HUMAN

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Protein
Phospholipid scramblase 4
Gene
PLSCR4, GIG43
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system.

Cofactori

Calcium or magnesium.1 Publication

GO - Molecular functioni

  1. CD4 receptor binding Source: UniProtKB
  2. calcium ion binding Source: UniProtKB
  3. enzyme binding Source: UniProtKB
  4. phospholipid scramblase activity Source: UniProtKB
  5. protein binding Source: UniProtKB

GO - Biological processi

  1. cellular response to lipopolysaccharide Source: Ensembl
  2. phospholipid scrambling Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid scramblase 4
Short name:
PL scramblase 4
Alternative name(s):
Ca(2+)-dependent phospholipid scramblase 4
Cell growth-inhibiting gene 43 protein
TRA1
Gene namesi
Name:PLSCR4
ORF Names:GIG43
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:16497. PLSCR4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 303303Cytoplasmic By similarity
Add
BLAST
Transmembranei304 – 32017Helical; Reviewed prediction
Add
BLAST
Topological domaini321 – 3299Extracellular By similarity

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi290 – 2901D → A: 50% decrease in scramblase activity in presence of Ca2+, and 40% decrease in scramblase activity in presence of Mg2+. 1 Publication

Organism-specific databases

PharmGKBiPA33422.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 329329Phospholipid scramblase 4
PRO_0000100792Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei83 – 831Phosphotyrosine; by ABL By similarity
Modified residuei88 – 881Phosphotyrosine; by ABL By similarity
Lipidationi250 – 2501S-palmitoyl cysteine Inferred
Lipidationi255 – 2551S-palmitoyl cysteine Inferred

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ9NRQ2.
PaxDbiQ9NRQ2.
PRIDEiQ9NRQ2.

PTM databases

PhosphoSiteiQ9NRQ2.

Expressioni

Tissue specificityi

Expressed in heart, brain, placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, uterus, small intestine and colon. Not detected in peripheral blood lymphocytes.

Gene expression databases

ArrayExpressiQ9NRQ2.
BgeeiQ9NRQ2.
CleanExiHS_PLSCR4.
GenevestigatoriQ9NRQ2.

Organism-specific databases

HPAiHPA002276.

Interactioni

Subunit structurei

Interacts with PDCD6.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Hoxa1P090224EBI-769257,EBI-3957603From a different organism.

Protein-protein interaction databases

BioGridi121357. 7 interactions.
IntActiQ9NRQ2. 16 interactions.
MINTiMINT-1443866.
STRINGi9606.ENSP00000347038.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3Q5UX-ray2.50B271-283[»]
ProteinModelPortaliQ9NRQ2.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9898Proline-rich domain (PRD) By similarity
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi18 – 258SH3-binding 1 Reviewed prediction
Motifi30 – 334WW-binding Reviewed prediction
Motifi41 – 499SH3-binding 2 Reviewed prediction
Motifi98 – 1069SH3-binding 3 Reviewed prediction

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi195 – 2028Cys-rich

Domaini

The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity By similarity.

Sequence similaritiesi

Keywords - Domaini

Repeat, SH3-binding, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG317744.
HOGENOMiHOG000237356.
HOVERGENiHBG019157.
InParanoidiQ9NRQ2.
OMAiNRYDIKN.
OrthoDBiEOG77T14X.
PhylomeDBiQ9NRQ2.
TreeFamiTF314939.

Family and domain databases

InterProiIPR005552. Scramblase.
[Graphical view]
PANTHERiPTHR23248. PTHR23248. 1 hit.
PfamiPF03803. Scramblase. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NRQ2-1) [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

MSGVVPTAPE QPAGEMENQT KPPDPRPDAP PEYNSHFLPG PPGTAVPPPT    50
GYPGGLPMGY YSPQQPSTFP LYQPVGGIHP VRYQPGKYPM PNQSVPITWM 100
PGPTPMANCP PGLEYLVQLD NIHVLQHFEP LEMMTCFETN NRYDIKNNSD 150
QMVYIVTEDT DDFTRNAYRT LRPFVLRVTD CMGREIMTMQ RPFRCTCCCF 200
CCPSARQELE VQCPPGVTIG FVAEHWNLCR AVYSIQNEKK ENVMRVRGPC 250
STYGCGSDSV FEVKSLDGIS NIGSIIRKWN GLLSAMADAD HFDIHFPLDL 300
DVKMKAMIFG ACFLIDFMYF ERSPPQRSR 329
Length:329
Mass (Da):37,005
Last modified:November 4, 2008 - v2
Checksum:i12BE86728D54F794
GO
Isoform 2 (identifier: Q9NRQ2-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: Missing.
     119-208: Missing.

Note: No experimental confirmation available.

Show »
Length:224
Mass (Da):24,797
Checksum:i55E36F0305DAB876
GO

Sequence cautioni

The sequence AAP97186.1 differs from that shown. Reason: Frameshift at positions 152, 155, 163 and 325.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti34 – 341N → S.2 Publications
Corresponds to variant rs3762685 [ dbSNP | Ensembl ].
VAR_011315
Natural varianti155 – 1551I → V.2 Publications
Corresponds to variant rs1061409 [ dbSNP | Ensembl ].
VAR_011316

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515Missing in isoform 2.
VSP_042931Add
BLAST
Alternative sequencei119 – 20890Missing in isoform 2.
VSP_042932Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti56 – 572LP → FL in AAP97186. 1 Publication
Sequence conflicti74 – 741P → S in AAT52217. 1 Publication
Sequence conflicti149 – 1491S → L in AAP97186. 1 Publication
Sequence conflicti163 – 1631F → V in AAP97186. 1 Publication
Sequence conflicti175 – 1751V → G in AAP97186. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF199023 mRNA. Translation: AAF89960.1.
AY550971 mRNA. Translation: AAT52217.1.
AK128442 mRNA. Translation: BAC87442.1.
AK290214 mRNA. Translation: BAF82903.1.
AL833760 mRNA. Translation: CAH56232.1.
AC092982 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78935.1.
BC028354 mRNA. Translation: AAH28354.1.
AF087887 mRNA. Translation: AAP97186.1. Sequence problems.
CCDSiCCDS3133.1. [Q9NRQ2-1]
CCDS54651.1. [Q9NRQ2-2]
RefSeqiNP_001121776.1. NM_001128304.1. [Q9NRQ2-1]
NP_001121777.1. NM_001128305.1. [Q9NRQ2-1]
NP_001121778.1. NM_001128306.1.
NP_001170775.1. NM_001177304.1. [Q9NRQ2-2]
NP_065086.2. NM_020353.2. [Q9NRQ2-1]
XP_005247711.1. XM_005247654.1. [Q9NRQ2-1]
XP_005247712.1. XM_005247655.1. [Q9NRQ2-1]
UniGeneiHs.477869.

Genome annotation databases

EnsembliENST00000354952; ENSP00000347038; ENSG00000114698. [Q9NRQ2-1]
ENST00000433593; ENSP00000415605; ENSG00000114698. [Q9NRQ2-2]
ENST00000446574; ENSP00000399315; ENSG00000114698. [Q9NRQ2-1]
ENST00000493382; ENSP00000419040; ENSG00000114698. [Q9NRQ2-1]
GeneIDi57088.
KEGGihsa:57088.
UCSCiuc003evt.4. human. [Q9NRQ2-1]
uc003evu.4. human. [Q9NRQ2-2]

Polymorphism databases

DMDMi212276457.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF199023 mRNA. Translation: AAF89960.1 .
AY550971 mRNA. Translation: AAT52217.1 .
AK128442 mRNA. Translation: BAC87442.1 .
AK290214 mRNA. Translation: BAF82903.1 .
AL833760 mRNA. Translation: CAH56232.1 .
AC092982 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78935.1 .
BC028354 mRNA. Translation: AAH28354.1 .
AF087887 mRNA. Translation: AAP97186.1 . Sequence problems.
CCDSi CCDS3133.1. [Q9NRQ2-1 ]
CCDS54651.1. [Q9NRQ2-2 ]
RefSeqi NP_001121776.1. NM_001128304.1. [Q9NRQ2-1 ]
NP_001121777.1. NM_001128305.1. [Q9NRQ2-1 ]
NP_001121778.1. NM_001128306.1.
NP_001170775.1. NM_001177304.1. [Q9NRQ2-2 ]
NP_065086.2. NM_020353.2. [Q9NRQ2-1 ]
XP_005247711.1. XM_005247654.1. [Q9NRQ2-1 ]
XP_005247712.1. XM_005247655.1. [Q9NRQ2-1 ]
UniGenei Hs.477869.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3Q5U X-ray 2.50 B 271-283 [» ]
ProteinModelPortali Q9NRQ2.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121357. 7 interactions.
IntActi Q9NRQ2. 16 interactions.
MINTi MINT-1443866.
STRINGi 9606.ENSP00000347038.

PTM databases

PhosphoSitei Q9NRQ2.

Polymorphism databases

DMDMi 212276457.

Proteomic databases

MaxQBi Q9NRQ2.
PaxDbi Q9NRQ2.
PRIDEi Q9NRQ2.

Protocols and materials databases

DNASUi 57088.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000354952 ; ENSP00000347038 ; ENSG00000114698 . [Q9NRQ2-1 ]
ENST00000433593 ; ENSP00000415605 ; ENSG00000114698 . [Q9NRQ2-2 ]
ENST00000446574 ; ENSP00000399315 ; ENSG00000114698 . [Q9NRQ2-1 ]
ENST00000493382 ; ENSP00000419040 ; ENSG00000114698 . [Q9NRQ2-1 ]
GeneIDi 57088.
KEGGi hsa:57088.
UCSCi uc003evt.4. human. [Q9NRQ2-1 ]
uc003evu.4. human. [Q9NRQ2-2 ]

Organism-specific databases

CTDi 57088.
GeneCardsi GC03M145910.
HGNCi HGNC:16497. PLSCR4.
HPAi HPA002276.
MIMi 607612. gene.
neXtProti NX_Q9NRQ2.
PharmGKBi PA33422.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG317744.
HOGENOMi HOG000237356.
HOVERGENi HBG019157.
InParanoidi Q9NRQ2.
OMAi NRYDIKN.
OrthoDBi EOG77T14X.
PhylomeDBi Q9NRQ2.
TreeFami TF314939.

Miscellaneous databases

GeneWikii PLSCR4.
GenomeRNAii 57088.
NextBioi 62887.
PROi Q9NRQ2.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9NRQ2.
Bgeei Q9NRQ2.
CleanExi HS_PLSCR4.
Genevestigatori Q9NRQ2.

Family and domain databases

InterProi IPR005552. Scramblase.
[Graphical view ]
PANTHERi PTHR23248. PTHR23248. 1 hit.
Pfami PF03803. Scramblase. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of three new members of the phospholipid scramblase gene family."
    Wiedmer T., Zhou Q., Kwoh D.Y., Sims P.J.
    Biochim. Biophys. Acta 1467:244-253(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SER-34 AND VAL-155.
    Tissue: Pancreas.
  2. "Identification of a human cell growth inhibiting gene."
    Kim J.W.
    Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS SER-34 AND VAL-155.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Thalamus and Thymus.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Stomach.
  5. "The DNA sequence, annotation and analysis of human chromosome 3."
    Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
    , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
    Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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] (ISOFORM 1).
    Tissue: Testis.
  8. "Cloning and characterization of a novel human cDNA homology to murine TRA1 mRNA."
    Cui W.C., Yu L., Gao J., Fan Y.X., Xu Y.F., Zhao S.Y.
    Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-329 (ISOFORM 1).
  9. "Identification of Alix-type and non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants."
    Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T., Maki M.
    J. Biol. Chem. 283:9623-9632(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PDCD6.
  10. "Biochemical and functional characterization of human phospholipid scramblase 4 (hPLSCR4)."
    Francis V.G., Gummadi S.N.
    Biol. Chem. 393:1173-1181(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: COFACTOR, MUTAGENESIS OF ASP-290.

Entry informationi

Entry nameiPLS4_HUMAN
AccessioniPrimary (citable) accession number: Q9NRQ2
Secondary accession number(s): A8K2E9
, Q2TTR3, Q658L3, Q6ZR73, Q7Z505
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: November 4, 2008
Last modified: September 3, 2014
This is version 123 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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