Q13094 (LCP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lymphocyte cytosolic protein 2

Alternative name(s):
SH2 domain-containing leukocyte protein of 76 kDa
SLP-76 tyrosine phosphoprotein
Short name=SLP76

Gene names

Name:

LCP2

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

General annotation (Comments)

Function	Involved in T-cell antigen receptor mediated signaling.
Subunit structure	Interacts with SLA. Interacts with CBLB By similarity. Interacts with the adapter proteins GRB2 and FYB. Interacts with SHB. Interacts with PRAM1. Ref.5 Ref.6
Subcellular location	Cytoplasm Probable.
Tissue specificity	Highly expressed in spleen, thymus and peripheral blood leukocytes. Highly expressed also in T-cell and monocytic cell lines, expressed at lower level in B-cell lines. Not detected in fibroblast or neuroblastoma cell lines.
Domain	The SH2 domain mediates interaction with SHB.
Post-translational modification	Phosphorylated after T-cell receptor activation by ZAP70, ITK and TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2. SYK-dependent phosphorylation is required for recruitment of PI3K signaling components. Ref.8 Ref.10
Sequence similarities	Contains 1 SAM (sterile alpha motif) domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell receptor signaling pathway Traceable author statement. Source: Reactome cytokine secretion Inferred from electronic annotation. Source: Compara immune response Traceable author statement Ref.1. Source: ProtInc mast cell activation Inferred from electronic annotation. Source: Compara platelet activation Traceable author statement. Source: Reactome transmembrane receptor protein tyrosine kinase signaling pathway Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAP4K3	Q8IVH8	5	EBI-346946,EBI-1758170
Map4k3	Q99JP0	2	EBI-346946,EBI-5324222	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 533

533

Lymphocyte cytosolic protein 2

PRO_0000084368

Regions

Domain

15 – 81

67

SAM

Domain

422 – 530

109

SH2

Compositional bias

133 – 136

4

Poly-Glu

Compositional bias

198 – 201

4

Poly-Pro

Amino acid modifications

Modified residue

23

1

Phosphotyrosine By similarity

Modified residue

207

1

Phosphoserine Ref.7 Ref.9

Secondary structure

1

.

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.

.

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533

Helix Strand Turn

Details...

Beta strand

1 – 4

4

Helix

9 – 12

4

Turn

17 – 19

3

Helix

20 – 26

7

Helix

30 – 38

9

Helix

43 – 47

5

Helix

51 – 54

4

Turn

59 – 61

3

Helix

62 – 73

12

Helix

237 – 239

3

Sequences

	Sequence		Length	Mass (Da)
	Q13094 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: C5D22F31D36200C8	FASTA	533	60,188
	10 20 30 40 50 60 MALRNVPFRS EVLGWDPDSL ADYFKKLNYK DCEKAVKKYH IDGARFLNLT ENDIQKFPKL 70 80 90 100 110 120 RVPILSKLSQ EINKNEERRS IFTRKPQVPR FPEETESHEE DNGGWSSFEE DDYESPNDDQ 130 140 150 160 170 180 DGEDDGDYES PNEEEEAPVE DDADYEPPPS NDEEALQNSI LPAKPFPNSN SMYIDRPPSG 190 200 210 220 230 240 KTPQQPPVPP QRPMAALPPP PAGRNHSPLP PPQTNHEEPS RSRNHKTAKL PAPSIDRSTK 250 260 270 280 290 300 PPLDRSLAPF DREPFTLGKK PPFSDKPSIP AGRSLGEHLP KIQKPPLPPT TERHERSSPL 310 320 330 340 350 360 PGKKPPVPKH GWGPDRREND EDDVHQRPLP QPALLPMSSN TFPSRSTKPS PMNPLPSSHM 370 380 390 400 410 420 PGAFSESNSS FPQSASLPPY FSQGPSNRPP IRAEGRNFPL PLPNKPRPPS PAEEENSLNE 430 440 450 460 470 480 EWYVSYITRP EAEAALRKIN QDGTFLVRDS SKKTTTNPYV LMVLYKDKVY NIQIRYQKES 490 500 510 520 530 QVYLLGTGLR GKEDFLSVSD IIDYFRKMPL LLIDGKNRGS RYQCTLTHAA GYP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells." Jackman J.K., Motto D.G., Sun Q., Tanemoto M., Turck C.W., Peltz G.A., Koretzky G.A., Findell P.R. J. Biol. Chem. 270:7029-7032(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Leukemia.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	Mural R.J., Istrail S., Sutton G.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].
[4]	"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]. Tissue: Prostate.
[5]	"PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells." Moog-Lutz C., Peterson E.J., Lutz P.G., Eliason S., Cave-Riant F., Singer A., Di Gioia Y., Dmovski S., Kamens J., Cayre Y.E., Koretzky G. J. Biol. Chem. 276:22375-22381(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRAM1.
[6]	"Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells." Lindholm C.K., Henriksson M.L., Hallberg B., Welsh M. Eur. J. Biochem. 269:3279-3288(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SHB.
[7]	"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-207, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase." Shim E.K., Moon C.S., Lee G.Y., Ha Y.J., Chae S.K., Lee J.R. FEBS Lett. 575:35-40(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY SYK.
[9]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207, MASS SPECTROMETRY. Tissue: Platelet.
[10]	"Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells." Sela M., Bogin Y., Beach D., Oellerich T., Lehne J., Smith-Garvin J.E., Okumura M., Starosvetsky E., Kosoff R., Libman E., Koretzky G., Kambayashi T., Urlaub H., Wienands J., Chernoff J., Yablonski D. EMBO J. 30:3160-3172(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY ITK.
[11]	"Solution structure of the N-terminal SAM-domain of human lymphocyte cytosolic protein 2." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-83.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U20158 mRNA. Translation: AAC50135.1.
BT007273 mRNA. Translation: AAP35937.1.
CH471062 Genomic DNA. Translation: EAW61479.1.
BC016618 mRNA. Translation: AAH16618.1.

IPI

IPI00297169.

PIR

A56110.

RefSeq

NP_005556.1. NM_005565.3.

UniGene

Hs.304475.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H3H	NMR	-	B	232-241	[»]
1YWO	X-ray	1.81	P	185-194	[»]
2EAP	NMR	-	A	1-83	[»]
2ROR	NMR	-	B	122-136	[»]

ProteinModelPortal

Q13094.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31812N.

IntAct

Q13094. 11 interactions.

MINT

MINT-110432.

STRING

9606.ENSP00000046794.

PTM databases

PhosphoSite

Q13094.

Polymorphism databases

DMDM

10720065.

Proteomic databases

PaxDb

Q13094.

PRIDE

Q13094.

Protocols and materials databases

DNASU

3937.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000046794; ENSP00000046794; ENSG00000043462.

GeneID

3937.

KEGG

hsa:3937.

UCSC

uc003man.1. human.

Organism-specific databases

CTD

3937.

GeneCards

GC05M169673.

H-InvDB

HIX0005402.

HGNC

HGNC:6529. LCP2.

HPA

CAB004574.
HPA036396.
HPA036397.

MIM

601603. gene.

neXtProt

NX_Q13094.

PharmGKB

PA30313.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG43557.

HOGENOM

HOG000049173.

HOVERGEN

HBG006247.

InParanoid

Q13094.

KO

K07361.

OMA

CEKAVKK.

OrthoDB

EOG4F1X2Z.

Enzyme and pathway databases

Pathway_Interaction_DB

fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
tcrjnkpathway. JNK signaling in the CD4+ TCR pathway.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13094.

Bgee

Q13094.

CleanEx

HS_LCP2.

Genevestigator

Q13094.

GermOnline

ENSG00000043462. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.
3.30.505.10. 1 hit.

InterPro

IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR000980. SH2.
[Graphical view]

Pfam

PF07647. SAM_2. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

SMART

SM00454. SAM. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

SUPFAM

SSF47769. SAM_homology. 1 hit.

PROSITE

PS50105. SAM_DOMAIN. False negative.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q13094.

GenomeRNAi

3937.

NextBio

15461.

SOURCE

Search...

Entry information

Entry name

LCP2_HUMAN

Accession

Primary (citable) accession number: Q13094
Secondary accession number(s): Q53XV4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 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.