P35329 (CD22_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
B-cell receptor CD22

Alternative name(s):
B-lymphocyte cell adhesion molecule
Short name=BL-CAM
Sialic acid-binding Ig-like lectin 2
Short name=Siglec-2
T-cell surface antigen Leu-14
CD_antigen=CD22

Gene names

Name:	Cd22
Synonyms:	Lyb-8, Siglec2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	862 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates B-cell B-cell interactions. May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site can be masked by cis interactions with sialic acids on the same cell surface. Upon ligand induced tyrosine phosphorylation in the immune response seems to be involved in regulation of B-cell antigen receptor signaling. Plays a role in positive regulation through interaction with Src family tyrosine kinases and may also act as an inhibitory receptor by recruiting cytoplasmic phosphatases via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules.
Subunit structure	Interacts with LYN, SYK, PIK3R1/PIK3R2, PLCG1, SHC1, INPP5D and GRB2 upon phosphorylation. May form a complex with INPP5D/SHIP, GRB2 and SHC1. Interacts with PTPN6/SHP-1 upon phosphorylation By similarity. Ref.6 Ref.7
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Tissue specificity	B-lymphocytes.
Domain	Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
Post-translational modification	Phosphorylated on tyrosine residues by LYN Probable. Ref.5 Ref.6 Ref.7 Phosphorylation of Tyr-777 and Tyr-837 are involved in binding to SYK. Phosphorylation of Tyr-822 is involved in binding to GRB2. Phosphorylation of Tyr-857 is involved in binding to SYK, PLCG2 and PIK3R1/PIK3R2.
Sequence similarities	Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family. Contains 6 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	Lectin
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell surface receptor signaling pathway Traceable author statement PubMed 11606382. Source: MGI
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 8418208. Source: MGI integral to plasma membrane Inferred from physical interaction PubMed 11606382. Source: MGI
Molecular_function	coreceptor activity Traceable author statement PubMed 11606382. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Grb2	Q60631	3	EBI-300059,EBI-1688

Alternative products

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

Isoform 1 (identifier: P35329-1)

Also known as: CD22-beta;

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: P35329-2)

The sequence of this isoform differs from the canonical sequence as follows:
     54-115: Missing.

Isoform 3 (identifier: P35329-3)

The sequence of this isoform differs from the canonical sequence as follows:
     100-133: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 862	841	B-cell receptor CD22		PRO_0000014874
Regions
	Topological domain	22 – 702	681	Extracellular Potential
	Transmembrane	703 – 721	19	Helical; Potential
	Topological domain	722 – 862	141	Cytoplasmic Potential
	Domain	22 – 142	121	Ig-like V-type
	Domain	147 – 244	98	Ig-like C2-type 1
	Domain	251 – 341	91	Ig-like C2-type 2
	Domain	346 – 429	84	Ig-like C2-type 3
	Domain	434 – 515	82	Ig-like C2-type 4
	Domain	520 – 597	78	Ig-like C2-type 5
	Domain	608 – 691	84	Ig-like C2-type 6
	Motif	775 – 780	6	ITIM motif 1
	Motif	835 – 840	6	ITIM motif 2
	Motif	855 – 860	6	ITIM motif 3
Sites
	Binding site	124	1	Sialic acid By similarity
Amino acid modifications
	Modified residue	777	1	Phosphotyrosine Probable
	Modified residue	822	1	Phosphotyrosine Probable
	Modified residue	837	1	Phosphotyrosine Probable
	Modified residue	857	1	Phosphotyrosine Probable
	Glycosylation	105	1	N-linked (GlcNAc...) Potential
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	139	1	N-linked (GlcNAc...) Potential
	Glycosylation	168	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	N-linked (GlcNAc...) Potential
	Glycosylation	275	1	N-linked (GlcNAc...) Potential
	Glycosylation	378	1	N-linked (GlcNAc...) Potential
	Glycosylation	408	1	N-linked (GlcNAc...) Potential
	Glycosylation	460	1	N-linked (GlcNAc...) Potential
	Glycosylation	561	1	N-linked (GlcNAc...) Potential
	Glycosylation	589	1	N-linked (GlcNAc...) Potential
	Disulfide bond	41 ↔ 171		By similarity
	Disulfide bond	46 ↔ 106		By similarity
	Disulfide bond	165 ↔ 229		By similarity
	Disulfide bond	272 ↔ 324		By similarity
	Disulfide bond	368 ↔ 411		By similarity
	Disulfide bond	457 ↔ 499		By similarity
	Disulfide bond	544 ↔ 586		By similarity
	Disulfide bond	631 ↔ 674		By similarity
Natural variations
	Alternative sequence	54 – 115	62	Missing in isoform 2.		VSP_002532
	Alternative sequence	100 – 133	34	Missing in isoform 3.		VSP_002533
	Natural variant	15	1	A → V in strain: BALB/c, C57BL/6, BXSB and MRL.
	Natural variant	19	1	Q → R in strain: BALB/c, C57BL/6, BXSB and MRL.
	Natural variant	76	1	K → T in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	83 – 86	4	KAEP → ATKTEKDPES in strain: BALB/c, C57BL/6, BXSB and MRL.
	Natural variant	90 – 91	2	PP → LS in strain: BALB/c.
	Natural variant	94	1	R → G in strain: BALB/c.
	Natural variant	102	1	S → R in strain: BALB/c, C57BL/6, BXSB and MRL.
	Natural variant	112 – 114	3	PIR → LIH in strain: BXSB.
	Natural variant	173	1	E → G in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	179	1	Q → K in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	186	1	K → E in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	190	1	V → I in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	192	1	P → S in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	236	1	E → K in strain: BALB/c, C57BL/6 and MRL.
	Natural variant	241	1	R → C in strain: BALB/c.
	Natural variant	244	1	R → H in strain: BALB/c and MRL.
	Natural variant	273	1	R → Q in strain: BXSB.
	Natural variant	380	1	T → I in strain: BXSB.
	Natural variant	387	1	P → H in strain: BXSB.
	Natural variant	403	1	P → L in strain: BXSB.
	Natural variant	419	1	H → R in strain: BXSB.
	Natural variant	423	1	D → G in strain: BXSB.
	Natural variant	482	1	P → S in strain: BXSB.
	Natural variant	548	1	E → K in strain: BXSB.
	Natural variant	616	1	S → I in strain: BALB/c.
	Natural variant	620	1	H → R in strain: BXSB.
	Natural variant	714	1	C → F in strain: BALB/c.
	Natural variant	787	1	M → T in strain: BALB/c, C57BL/6, BXSB and MRL.
	Natural variant	790	1	A → T in strain: C57BL/6.
	Natural variant	808	1	S → T in strain: BALB/c, BXSB and MRL.
Experimental info
	Mutagenesis	822	1	Y → F: Abolishes binding to GRB2. Ref.6
	Sequence conflict	87	1	E → G in CAB85611. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CD22-beta) [UniParc]. Last modified February 1, 1994. Version 1. Checksum: A7662D6E87038E83	FASTA	862	96,582
	10 20 30 40 50 60 MRVHYLWLLL ILGHAASAQY SSANDWTVDH PQTLFAWEGA CIRIPCKYKT PLPKARLDNI 70 80 90 100 110 120 LLFQNYEFDK ATKKFKGTVL YNKAEPELYP PKQRRVTFLG NSIDNCTLKI HPIRANDSGN 130 140 150 160 170 180 LGLRMTAGTE RWMEPIHLNV SEKPFQPYIQ MPSEIRESQS VTLTCGLNFS CFEYDILLQW 190 200 210 220 230 240 FLEDSKITSV TPSVTSITSS VTSSIKNVYT ESKLTFQPKW TDHGKSVKCQ VQHSSEVLSE 250 260 270 280 290 300 RTVRLDVKYT PKLEIKVNPT EVEKNNSVTM TCRVNSSNPK LRTVAVSWFK DGRPLEDQEL 310 320 330 340 350 360 EQEQQMSKLI LHSVTKDMRG KYRCQASNDI GPGESEEVEL TVHYAPEPSR VHIYPSPAEE 370 380 390 400 410 420 GQSVELICES LASPSATNYT WYHNRKPIPG DTQEKLRIPK VSPWHAGNYS CLAENRLGHG 430 440 450 460 470 480 KIDQEAKLDV HYAPKAVTTV IQSFTPILEG DSVTLVCRYN SSNPDVTSYR WNPQGSGSVL 490 500 510 520 530 540 KPGVLRIQKV TWDSMPVSCA ACNHKCSWAL PVILNVHYAP RDVKVLKVSP ASEIRAGQRV 550 560 570 580 590 600 LLQCDFAESN PAEVRFFWKK NGSLVQEGRY LSFGSVSPED SGNYNCMVNN SIGETLSQAW 610 620 630 640 650 660 NLQVLYAPRR LRVSISPGDH VMEGKKATLS CESDANPPIS QYTWFDSSGQ DLHSSGQKLR 670 680 690 700 710 720 LEPLEVQHTG SYRCKGTNGI GTGESPPSTL TVYYSPETIG KRVALGLGFC LTICILAIWG 730 740 750 760 770 780 MKIQKKWKQN RSQQGLQENS SGQSFFVRNK KARRTPLSEG PQSQGCYNPA MDDTVSYAIL 790 800 810 820 830 840 RFPESDMHNA GDAGTPATQA PPPNNSDSVT YSVIQKRPMG DYENVNPSCP EDESIHYSEL 850 860 VQFGAGKRPQ AKEDVDYVTL KH
	Isoform 2 [UniParc]. Checksum: 394094553D0F14E6	FASTA	800	89,333
	10 20 30 40 50 60 MRVHYLWLLL ILGHAASAQY SSANDWTVDH PQTLFAWEGA CIRIPCKYKT PLPNDSGNLG 70 80 90 100 110 120 LRMTAGTERW MEPIHLNVSE KPFQPYIQMP SEIRESQSVT LTCGLNFSCF EYDILLQWFL 130 140 150 160 170 180 EDSKITSVTP SVTSITSSVT SSIKNVYTES KLTFQPKWTD HGKSVKCQVQ HSSEVLSERT 190 200 210 220 230 240 VRLDVKYTPK LEIKVNPTEV EKNNSVTMTC RVNSSNPKLR TVAVSWFKDG RPLEDQELEQ 250 260 270 280 290 300 EQQMSKLILH SVTKDMRGKY RCQASNDIGP GESEEVELTV HYAPEPSRVH IYPSPAEEGQ 310 320 330 340 350 360 SVELICESLA SPSATNYTWY HNRKPIPGDT QEKLRIPKVS PWHAGNYSCL AENRLGHGKI 370 380 390 400 410 420 DQEAKLDVHY APKAVTTVIQ SFTPILEGDS VTLVCRYNSS NPDVTSYRWN PQGSGSVLKP 430 440 450 460 470 480 GVLRIQKVTW DSMPVSCAAC NHKCSWALPV ILNVHYAPRD VKVLKVSPAS EIRAGQRVLL 490 500 510 520 530 540 QCDFAESNPA EVRFFWKKNG SLVQEGRYLS FGSVSPEDSG NYNCMVNNSI GETLSQAWNL 550 560 570 580 590 600 QVLYAPRRLR VSISPGDHVM EGKKATLSCE SDANPPISQY TWFDSSGQDL HSSGQKLRLE 610 620 630 640 650 660 PLEVQHTGSY RCKGTNGIGT GESPPSTLTV YYSPETIGKR VALGLGFCLT ICILAIWGMK 670 680 690 700 710 720 IQKKWKQNRS QQGLQENSSG QSFFVRNKKA RRTPLSEGPQ SQGCYNPAMD DTVSYAILRF 730 740 750 760 770 780 PESDMHNAGD AGTPATQAPP PNNSDSVTYS VIQKRPMGDY ENVNPSCPED ESIHYSELVQ 790 800 FGAGKRPQAK EDVDYVTLKH
	Isoform 3 [UniParc]. Checksum: 6C84F4BE3F0B6045	FASTA	828	92,857
	10 20 30 40 50 60 MRVHYLWLLL ILGHAASAQY SSANDWTVDH PQTLFAWEGA CIRIPCKYKT PLPKARLDNI 70 80 90 100 110 120 LLFQNYEFDK ATKKFKGTVL YNKAEPELYP PKQRRVTFLE PIHLNVSEKP FQPYIQMPSE 130 140 150 160 170 180 IRESQSVTLT CGLNFSCFEY DILLQWFLED SKITSVTPSV TSITSSVTSS IKNVYTESKL 190 200 210 220 230 240 TFQPKWTDHG KSVKCQVQHS SEVLSERTVR LDVKYTPKLE IKVNPTEVEK NNSVTMTCRV 250 260 270 280 290 300 NSSNPKLRTV AVSWFKDGRP LEDQELEQEQ QMSKLILHSV TKDMRGKYRC QASNDIGPGE 310 320 330 340 350 360 SEEVELTVHY APEPSRVHIY PSPAEEGQSV ELICESLASP SATNYTWYHN RKPIPGDTQE 370 380 390 400 410 420 KLRIPKVSPW HAGNYSCLAE NRLGHGKIDQ EAKLDVHYAP KAVTTVIQSF TPILEGDSVT 430 440 450 460 470 480 LVCRYNSSNP DVTSYRWNPQ GSGSVLKPGV LRIQKVTWDS MPVSCAACNH KCSWALPVIL 490 500 510 520 530 540 NVHYAPRDVK VLKVSPASEI RAGQRVLLQC DFAESNPAEV RFFWKKNGSL VQEGRYLSFG 550 560 570 580 590 600 SVSPEDSGNY NCMVNNSIGE TLSQAWNLQV LYAPRRLRVS ISPGDHVMEG KKATLSCESD 610 620 630 640 650 660 ANPPISQYTW FDSSGQDLHS SGQKLRLEPL EVQHTGSYRC KGTNGIGTGE SPPSTLTVYY 670 680 690 700 710 720 SPETIGKRVA LGLGFCLTIC ILAIWGMKIQ KKWKQNRSQQ GLQENSSGQS FFVRNKKARR 730 740 750 760 770 780 TPLSEGPQSQ GCYNPAMDDT VSYAILRFPE SDMHNAGDAG TPATQAPPPN NSDSVTYSVI 790 800 810 820 QKRPMGDYEN VNPSCPEDES IHYSELVQFG AGKRPQAKED VDYVTLKH

References

[1]	"Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles." Law C.-L., Torres R.M., Sundberg H.A., Parkhouse R.M., Brannan C.I., Copeland N.G., Jenkins N.A., Clark E.A. J. Immunol. 151:175-187(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c and DBA/2J. Tissue: Liver.
[2]	"Polymorphisms in the Cd22 gene of inbred mouse strains." Lajaunias F., Ibnou-Zekri N., Fossati Jimack L., Chicheportiche Y., Parkhouse R.M., Mary C., Reininger L., Brighouse G., Izui S. Immunogenetics 49:991-995(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BXSB, C57BL/6 and MRL.
[3]	"Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22alpha lupus-prone mice." Mary C., Laporte C., Parzy D., Santiago M.L., Stefani F., Lajaunias F., Parkhouse M.E., O'Keefe T.L., Neuberger M.S., Izui S., Reininger L. J. Immunol. 165:2987-2996(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-178 (ISOFORMS 1; 2 AND 3). Strain: NZW. Tissue: Spleen.
[4]	"Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily." Kelm S., Pelz A., Schauer R., Filbin M.T., Tang S., de Bellard M.E., Schnaar R.L., Mahoney J.A., Hartnell A., Bradfield P., Crocker P.R. Curr. Biol. 4:965-972(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SIALIC ACID-BINDING.
[5]	"Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes." Chan V.W., Lowell C.A., DeFranco A.L. Curr. Biol. 8:545-553(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY LYN.
[6]	"Analysis of tyrosine phosphorylation-dependent interactions between stimulatory effector proteins and the B cell co-receptor CD22." Yohannan J., Wienands J., Coggeshall K.M., Justement L.B. J. Biol. Chem. 274:18769-18776(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB2; SYK; PIK3R1/PIK3R2 AND PLCG1, PHOSPHORYLATION AT TYR-777; TYR-822; TYR-837 AND TYR-857, MUTAGENESIS OF TYR-822.
[7]	"CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux." Poe J.C., Fujimoto M., Jansen P.J., Miller A.S., Tedder T.F. J. Biol. Chem. 275:17420-17427(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB2; SHC1 AND INPP5D, PHOSPHORYLATION BY LYN.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Siglec-2

Cross-references

Sequence databases
EMBL GenBank DDBJ	L16928 mRNA. Translation: AAA02562.1. AF115401 mRNA. Translation: AAD30392.1. AF115400 mRNA. Translation: AAD30391.1. AF102134 mRNA. Translation: AAF02417.1. AJ250676 mRNA. Translation: CAB85609.1. AJ250677 mRNA. Translation: CAB85610.1. AJ250678 mRNA. Translation: CAB85611.1. AJ250679 mRNA. Translation: CAB85612.1. AJ250680 mRNA. Translation: CAB85613.1. AJ250682 mRNA. Translation: CAB85615.1. AJ250683 mRNA. Translation: CAB85616.1.
IPI	IPI00117413. IPI00228046. IPI00228047.
PIR	A46512. I49583.
RefSeq	NP_001036782.1. NM_001043317.2. NP_033975.3. NM_009845.3.
UniGene	Mm.260994.
3D structure databases
ProteinModelPortal	P35329.
SMR	P35329. Positions 38-692.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35329. 7 interactions.
PTM databases
PhosphoSite	P35329.
Proteomic databases
PaxDb	P35329.
PRIDE	P35329.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	12483.
KEGG	mmu:12483.
Organism-specific databases
CTD	933.
MGI	MGI:88322. Cd22.
Phylogenomic databases
eggNOG	NOG287433.
HOVERGEN	HBG005272.
InParanoid	P35329.
KO	K06467.
OrthoDB	EOG4C87RQ.
Gene expression databases
CleanEx	MM_CD22.
Genevestigator	P35329.
GermOnline	ENSMUSG00000030577. Mus musculus.
Family and domain databases
Gene3D	2.60.40.10. 6 hits.
InterPro	IPR013162. CD80_C2-set. IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR003598. Ig_sub2. [Graphical view]
Pfam	PF08205. C2-set_2. 1 hit. [Graphical view]
SMART	SM00409. IG. 2 hits. SM00408. IGc2. 4 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 6 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P35329.
ChEMBL	CHEMBL1075279.
NextBio	281386.
SOURCE	Search...

Entry information

Entry name

CD22_MOUSE

Accession

Primary (citable) accession number: P35329
Secondary accession number(s): Q9JHL2 , Q9JJX9, Q9JJY0, Q9JJY1, Q9R056, Q9R094, Q9WU51

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program