Q9NRQ2 (PLS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PLSCR4
ORF Names:	GIG43

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

General annotation (Comments)

Function	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.
Cofactor	Calcium or magnesium. Ref.10
Subunit structure	Interacts with PDCD6. Ref.9
Subcellular location	Membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	Expressed in heart, brain, placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, uterus, small intestine and colon. Not detected in peripheral blood lymphocytes.
Sequence similarities	Belongs to the phospholipid scramblase family.
Sequence caution	The sequence AAP97186.1 differs from that shown. Reason: Frameshift at positions 152, 155, 163 and 325.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH3-binding Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Non-traceable author statement. Source: UniProtKB cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara phospholipid scrambling Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to membrane Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from direct assay PubMed 19333378. Source: UniProtKB
Molecular_function	calcium ion binding Non-traceable author statement Ref.1. Source: UniProtKB phospholipid scramblase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hoxa1	P09022	4	EBI-769257,EBI-3957603	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NRQ2-1)

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: Q9NRQ2-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 329	329	Phospholipid scramblase 4		PRO_0000100792
Regions
	Topological domain	1 – 303	303	Cytoplasmic By similarity
	Transmembrane	304 – 320	17	Helical; Potential
	Topological domain	321 – 329	9	Extracellular By similarity
	Motif	18 – 25	8	SH3-binding 1 Potential
	Motif	30 – 33	4	WW-binding Potential
	Motif	41 – 49	9	SH3-binding 2 Potential
	Motif	98 – 106	9	SH3-binding 3 Potential
	Compositional bias	195 – 202	8	Cys-rich
Amino acid modifications
	Modified residue	83	1	Phosphotyrosine; by ABL By similarity
	Modified residue	88	1	Phosphotyrosine; by ABL By similarity
	Lipidation	250	1	S-palmitoyl cysteine Probable
	Lipidation	255	1	S-palmitoyl cysteine Probable
Natural variations
	Alternative sequence	1 – 15	15	Missing in isoform 2.		VSP_042931
	Alternative sequence	119 – 208	90	Missing in isoform 2.		VSP_042932
	Natural variant	34	1	N → S. Ref.1 Ref.2 Corresponds to variant rs3762685 [ dbSNP | Ensembl ].		VAR_011315
	Natural variant	155	1	I → V. Ref.1 Ref.2 Corresponds to variant rs1061409 [ dbSNP | Ensembl ].		VAR_011316
Experimental info
	Mutagenesis	290	1	D → A: 50% decrease in scramblase activity in presence of Ca2+, and 40% decrease in scramblase activity in presence of Mg2+. Ref.10
	Sequence conflict	56 – 57	2	LP → FL in AAP97186. Ref.8
	Sequence conflict	74	1	P → S in AAT52217. Ref.2
	Sequence conflict	149	1	S → L in AAP97186. Ref.8
	Sequence conflict	163	1	F → V in AAP97186. Ref.8
	Sequence conflict	175	1	V → G in AAP97186. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: 12BE86728D54F794	FASTA	329	37,005
	10 20 30 40 50 60 MSGVVPTAPE QPAGEMENQT KPPDPRPDAP PEYNSHFLPG PPGTAVPPPT GYPGGLPMGY 70 80 90 100 110 120 YSPQQPSTFP LYQPVGGIHP VRYQPGKYPM PNQSVPITWM PGPTPMANCP PGLEYLVQLD 130 140 150 160 170 180 NIHVLQHFEP LEMMTCFETN NRYDIKNNSD QMVYIVTEDT DDFTRNAYRT LRPFVLRVTD 190 200 210 220 230 240 CMGREIMTMQ RPFRCTCCCF CCPSARQELE VQCPPGVTIG FVAEHWNLCR AVYSIQNEKK 250 260 270 280 290 300 ENVMRVRGPC STYGCGSDSV FEVKSLDGIS NIGSIIRKWN GLLSAMADAD HFDIHFPLDL 310 320 DVKMKAMIFG ACFLIDFMYF ERSPPQRSR
	Isoform 2 [UniParc]. Checksum: 55E36F0305DAB876	FASTA	224	24,797
	10 20 30 40 50 60 MENQTKPPDP RPDAPPEYNS HFLPGPPGTA VPPPTGYPGG LPMGYYSPQQ PSTFPLYQPV 70 80 90 100 110 120 GGIHPVRYQP GKYPMPNQSV PITWMPGPTP MANCPPGLEY LVQLEVQCPP GVTIGFVAEH 130 140 150 160 170 180 WNLCRAVYSI QNEKKENVMR VRGPCSTYGC GSDSVFEVKS LDGISNIGSI IRKWNGLLSA 190 200 210 220 MADADHFDIH FPLDLDVKMK AMIFGACFLI DFMYFERSPP QRSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] 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]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00016776.
IPI00945326.

RefSeq

NP_001121776.1. NM_001128304.1.
NP_001121777.1. NM_001128305.1.
NP_001121778.1. NM_001128306.1.
NP_001170775.1. NM_001177304.1.
NP_065086.2. NM_020353.2.

UniGene

Hs.477869.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3Q5U	X-ray	2.50	B	271-283	[»]

ProteinModelPortal

Q9NRQ2.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NRQ2. 14 interactions.

MINT

MINT-1443866.

STRING

9606.ENSP00000347038.

PTM databases

PhosphoSite

Q9NRQ2.

Polymorphism databases

DMDM

212276457.

Proteomic databases

PaxDb

Q9NRQ2.

PRIDE

Q9NRQ2.

Protocols and materials databases

DNASU

57088.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000354952; ENSP00000347038; ENSG00000114698.
ENST00000433593; ENSP00000415605; ENSG00000114698.
ENST00000446574; ENSP00000399315; ENSG00000114698.
ENST00000493382; ENSP00000419040; ENSG00000114698.

GeneID

57088.

KEGG

hsa:57088.

UCSC

uc003evt.4. human.

Organism-specific databases

CTD

57088.

GeneCards

GC03M145910.

HGNC

HGNC:16497. PLSCR4.

HPA

HPA002276.

MIM

607612. gene.

neXtProt

NX_Q9NRQ2.

PharmGKB

PA33422.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG317744.

HOGENOM

HOG000237356.

HOVERGEN

HBG019157.

InParanoid

Q9NRQ2.

OMA

MKAMIFG.

OrthoDB

EOG43FGXC.

PhylomeDB

Q9NRQ2.

Gene expression databases

ArrayExpress

Q9NRQ2.

Bgee

Q9NRQ2.

CleanEx

HS_PLSCR4.

Genevestigator

Q9NRQ2.

GermOnline

ENSG00000114698. Homo sapiens.

Family and domain databases

InterPro

IPR005552. Scramblase.
[Graphical view]

PANTHER

PTHR23248. PTHR23248. 1 hit.

Pfam

PF03803. Scramblase. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

57088.

NextBio

62887.

SOURCE

Search...

Entry information

Entry name

PLS4_HUMAN

Accession

Primary (citable) accession number: Q9NRQ2
Secondary accession number(s): A8K2E9 , Q2TTR3, Q658L3, Q6ZR73, Q7Z505

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	November 4, 2008
Last modified:	April 3, 2013
This is version 110 of the entry and version 2 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.