Reviewed, UniProtKB/Swiss-Prot Q5QGZ9 (CL12A_HUMAN)

Names and origin

Protein names

Recommended name:
    C-type lectin domain family 12 member A
Alternative name(s):
    Myeloid inhibitory C-type lectin-like receptor
      Short name=MICL
    C-type lectin-like molecule 1
      Short name=CLL-1
    Dendritic cell-associated lectin 2
      Short name=DCAL-2

Gene names

Name:	CLEC12A
Synonyms:	CLL1, DCAL2, MICL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	275 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases.
Subunit structure	Interacts with PTPN6 and PTPN11.
Subcellular location	Cell membrane; Single-pass type II membrane protein. Note= Ligand binding leads to internalization.
Tissue specificity	Detected in normal myeloid cells and in acute myeloid leukemia cells. Detected in neutrophils, eosinophils, monocytes and dendritic cells. Detected in spleen macrophage-rich red pulp and in lymph node (at protein level). Detected in peripheral blood leukocytes, dendritic cells, bone marrow, monocytes, mononuclear leukocytes and macrophages.
Induction	Down-regulated in activated leukocytes recruited to a site of inflammation.
Domain	Contains 1 copy 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	Highly N-glycosylated. Glycosylation varies between cell types.
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane
Ligand	Lectin
Molecular function	Receptor
PTM	Glycoprotein
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	receptor activity Inferred from electronic annotation. Source: UniProtKB-KW sugar binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5QGZ9-1)

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: Q5QGZ9-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: Missing.

Isoform 3 (identifier: Q5QGZ9-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: Missing.
     74-91: FHVTLKIEMKKMNKLQNI → CMYCPCFGQEEVSRISNI
     92-275: Missing.

Isoform 4 (identifier: Q5QGZ9-4)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: Missing.
     41-74: APPAPSHVWRPAALFLTLLCLLLLIGLGVLASMF → V

Isoform 5 (identifier: Q5QGZ9-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: Missing.
     224-275: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 275	275	C-type lectin domain family 12 member A		PRO_0000313578
Regions
	Topological domain	1 – 53	53	Cytoplasmic Potential
	Transmembrane	54 – 74	21	Signal-anchor for type II membrane protein Potential
	Topological domain	75 – 275	201	Extracellular Potential
	Domain	150 – 259	110	C-type lectin
	Motif	15 – 20	6	ITIM motif
Amino acid modifications
	Glycosylation	98	1	N-linked (GlcNAc...) Potential
	Glycosylation	108	1	N-linked (GlcNAc...)
	Glycosylation	175	1	N-linked (GlcNAc...) Potential
	Disulfide bond	171 ↔ 258		By similarity
	Disulfide bond	237 ↔ 250		By similarity
Natural variations
	Alternative sequence	1 – 10	10	Missing in isoform 2, isoform 3, isoform 4 and isoform 5.		VSP_030029
	Alternative sequence	41 – 74	34	APPAP…LASMF → V in isoform 4.		VSP_030030
	Alternative sequence	74 – 91	18	FHVTL…KLQNI → CMYCPCFGQEEVSRISNI in isoform 3.		VSP_030031
	Alternative sequence	92 – 275	184	Missing in isoform 3.		VSP_030032
	Alternative sequence	224 – 275	52	Missing in isoform 5.		VSP_030033
	Natural variant	254	1	Q → K: dbSNP rs479499.		VAR_037669

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: 71AA82DBDD134228	FASTA	275	32,040
	10 20 30 40 50 60 MWIDFFTYSS MSEEVTYADL QFQNSSEMEK IPEIGKFGEK APPAPSHVWR PAALFLTLLC 70 80 90 100 110 120 LLLLIGLGVL ASMFHVTLKI EMKKMNKLQN ISEELQRNIS LQLMSNMNIS NKIRNLSTTL 130 140 150 160 170 180 QTIATKLCRE LYSKEQEHKC KPCPRRWIWH KDSCYFLSDD VQTWQESKMA CAAQNASLLK 190 200 210 220 230 240 INNKNALEFI KSQSRSYDYW LGLSPEEDST RGMRVDNIIN SSAWVIRNAP DLNNMYCGYI 250 260 270 NRLYVQYYHC TYKQRMICEK MANPVQLGST YFREA
	Isoform 2 (Alpha) [UniParc]. Checksum: 4255FF1EA9E00ED1		265	30,762
	10 20 30 40 50 60 MSEEVTYADL QFQNSSEMEK IPEIGKFGEK APPAPSHVWR PAALFLTLLC LLLLIGLGVL 70 80 90 100 110 120 ASMFHVTLKI EMKKMNKLQN ISEELQRNIS LQLMSNMNIS NKIRNLSTTL QTIATKLCRE 130 140 150 160 170 180 LYSKEQEHKC KPCPRRWIWH KDSCYFLSDD VQTWQESKMA CAAQNASLLK INNKNALEFI 190 200 210 220 230 240 KSQSRSYDYW LGLSPEEDST RGMRVDNIIN SSAWVIRNAP DLNNMYCGYI NRLYVQYYHC 250 260 TYKQRMICEK MANPVQLGST YFREA
	Isoform 3 (Gamma) [UniParc]. Checksum: F025075C173112DD		81	8,965
	10 20 30 40 50 60 MSEEVTYADL QFQNSSEMEK IPEIGKFGEK APPAPSHVWR PAALFLTLLC LLLLIGLGVL 70 80 ASMCMYCPCF GQEEVSRISN I
	Isoform 4 (Beta) [UniParc]. Checksum: 3BF3147C5CFB9125		232	27,276
	10 20 30 40 50 60 MSEEVTYADL QFQNSSEMEK IPEIGKFGEK VHVTLKIEMK KMNKLQNISE ELQRNISLQL 70 80 90 100 110 120 MSNMNISNKI RNLSTTLQTI ATKLCRELYS KEQEHKCKPC PRRWIWHKDS CYFLSDDVQT 130 140 150 160 170 180 WQESKMACAA QNASLLKINN KNALEFIKSQ SRSYDYWLGL SPEEDSTRGM RVDNIINSSA 190 200 210 220 230 WVIRNAPDLN NMYCGYINRL YVQYYHCTYK QRMICEKMAN PVQLGSTYFR EA
	Isoform 5 [UniParc]. Checksum: D026446C70B23B77		213	24,449
	10 20 30 40 50 60 MSEEVTYADL QFQNSSEMEK IPEIGKFGEK APPAPSHVWR PAALFLTLLC LLLLIGLGVL 70 80 90 100 110 120 ASMFHVTLKI EMKKMNKLQN ISEELQRNIS LQLMSNMNIS NKIRNLSTTL QTIATKLCRE 130 140 150 160 170 180 LYSKEQEHKC KPCPRRWIWH KDSCYFLSDD VQTWQESKMA CAAQNASLLK INNKNALEFI 190 200 210 KSQSRSYDYW LGLSPEEDST RGMRVDNIIN SSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"C-type lectin-like molecule-1: a novel myeloid cell surface marker associated with acute myeloid leukemia." Bakker A.B.H., van den Oudenrijn S., Bakker A.Q., Feller N., van Meijer M., Bia J.A., Jongeneelen M.A.C., Visser T.J., Bijl N., Geuijen C.A.W., Marissen W.E., Radosevic K., Throsby M., Schuurhuis G.J., Ossenkoppele G.J., de Kruif J., Goudsmit J., Kruisbeek A.M. Cancer Res. 64:8443-8450(2004) [PubMed: 15548716] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Bone marrow.
[2]	"Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes." Marshall A.S.J., Willment J.A., Lin H.-H., Williams D.L., Gordon S., Brown G.D. J. Biol. Chem. 279:14792-14802(2004) [PubMed: 14739280] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), VARIANT LYS-254, FUNCTION, INTERACTION WITH PTPN6 AND PTPN11, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY.
[3]	"Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production." Chen C.-H., Floyd H., Olson N.E., Magaletti D., Li C., Draves K., Clark E.A. Blood 107:1459-1467(2006) [PubMed: 16239426] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Novel human C-type lectin superfamily member CLL-1." Zhang W., Wan T., Chen T., Cao X. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5). Tissue: Blood.
[7]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-108, MASS SPECTROMETRY. Tissue: Plasma.
[8]	"Human MICL (CLEC12A) is differentially glycosylated and is down-regulated following cellular activation." Marshall A.S.J., Willment J.A., Pyz E., Dennehy K.M., Reid D.M., Dri P., Gordon S., Wong S.Y.C., Brown G.D. Eur. J. Immunol. 36:2159-2169(2006) [PubMed: 16838277] [Abstract] Cited for: GLYCOSYLATION, INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY547296 mRNA. Translation: AAT11783.1. AY498550 mRNA. Translation: AAS00605.1. AY498551 mRNA. Translation: AAS00606.1. AY498552 mRNA. Translation: AAS00607.1. AY426759 mRNA. Translation: AAR84594.1. AF247788 mRNA. Translation: AAL95693.1. CH471094 Genomic DNA. Translation: EAW96133.1. BC063424 mRNA. Translation: AAH63424.1. BC126289 mRNA. Translation: AAI26290.1. BC126291 mRNA. Translation: AAI26292.1.
RefSeq	NP_612210.4. NP_963917.2.
UniGene	Hs.190519
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000172322. Homo sapiens. [Contig view]
GeneID	160364.
Organism-specific databases
HGNC	HGNC:31713. CLEC12A.
MIM	612088. gene.
PharmGKB	PA142672094.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q5QGZ9.
HOVERGEN	Q5QGZ9.
Gene expression databases
ArrayExpress	Q5QGZ9.
CleanEx	HS_CLEC12A.
Family and domain databases
InterPro	IPR001304. C-type_lectin. IPR016186. C-type_lectin-like. [Graphical view]
Gene3D	G3DSA:3.10.100.10. C-type_lectin-like. 1 hit.
Pfam	PF00059. Lectin_C. 1 hit. [Graphical view]
SMART	SM00034. CLECT. 1 hit. [Graphical view]
PROSITE	PS00615. C_TYPE_LECTIN_1. False negative. PS50041. C_TYPE_LECTIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

CL12A_HUMAN

Accession

Primary (citable) accession number: Q5QGZ9
Secondary accession number(s): Q6P4H1 , Q6RH77, Q6RH78, Q8TDQ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	January 15, 2008
Last modified:	November 4, 2008
This is version 31 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)