Q5QGZ9 (CL12A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-type lectin domain family 12 member A

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

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	265 AA.
Sequence status	Complete.
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. Ref.2 Ref.3
Subunit structure	Interacts with PTPN6 and PTPN11. Ref.2
Subcellular location	Cell membrane; Single-pass type II membrane protein. Note: Ligand binding leads to internalization. Ref.1 Ref.2 Ref.3 Ref.10
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. Ref.1 Ref.2 Ref.3 Ref.10
Induction	Down-regulated in activated leukocytes recruited to a site of inflammation. Ref.10
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. Ref.2 Ref.9 Ref.10
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 Transmembrane helix
Ligand	Lectin
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
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 2 (identifier: Q5QGZ9-2)

Also known as: Alpha;

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 1 (identifier: Q5QGZ9-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MWIDFFTYSSM

Isoform 3 (identifier: Q5QGZ9-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     64-81: FHVTLKIEMKKMNKLQNI → CMYCPCFGQEEVSRISNI
     82-265: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 4 (identifier: Q5QGZ9-4)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     31-64: APPAPSHVWRPAALFLTLLCLLLLIGLGVLASMF → V

Isoform 5 (identifier: Q5QGZ9-5)

The sequence of this isoform differs from the canonical sequence as follows:
     214-265: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 265	265	C-type lectin domain family 12 member A		PRO_0000313578
Regions
	Topological domain	1 – 43	43	Cytoplasmic Potential
	Transmembrane	44 – 64	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	65 – 265	201	Extracellular Potential
	Domain	140 – 249	110	C-type lectin
	Motif	5 – 10	6	ITIM motif
Amino acid modifications
	Glycosylation	88	1	N-linked (GlcNAc...) Potential
	Glycosylation	98	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	165	1	N-linked (GlcNAc...) Potential
	Disulfide bond	161 ↔ 248		By similarity
	Disulfide bond	227 ↔ 240		By similarity
Natural variations
	Alternative sequence	1	1	M → MWIDFFTYSSM in isoform 1.		VSP_039854
	Alternative sequence	31 – 64	34	APPAP…LASMF → V in isoform 4.		VSP_030030
	Alternative sequence	64 – 81	18	FHVTL…KLQNI → CMYCPCFGQEEVSRISNI in isoform 3.		VSP_030031
	Alternative sequence	82 – 265	184	Missing in isoform 3.		VSP_030032
	Alternative sequence	214 – 265	52	Missing in isoform 5.		VSP_030033
	Natural variant	244	1	K → Q. Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Corresponds to variant rs479499 [ dbSNP | Ensembl ].		VAR_037669

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Alpha) [UniParc]. Last modified October 5, 2010. Version 3. Checksum: 4255FF1EA9F0D4B1	FASTA	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 TYKKRMICEK MANPVQLGST YFREA
	Isoform 1 [UniParc]. Checksum: 71AA82DBDD039848	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 TYKKRMICEK MANPVQLGST YFREA
	Isoform 3 (Gamma) [UniParc]. Checksum: F025075C173112DD	FASTA	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: 3BF3147C5CEB4B45	FASTA	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 KRMICEKMAN PVQLGSTYFR EA
	Isoform 5 [UniParc]. Checksum: D026446C70B23B77	FASTA	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 2; 3 AND 4), FUNCTION, INTERACTION WITH PTPN6 AND PTPN11, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY, VARIANT GLN-244.
[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, VARIANT GLN-244.
[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), VARIANT GLN-244.
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-244. Tissue: Lung.
[6]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., 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., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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], VARIANT GLN-244.
[8]	"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), VARIANT GLN-244. Tissue: Blood.
[9]	"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-98, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AK314001 mRNA. Translation: BAG36713.1. AC091814 Genomic DNA. No translation available. CH471094 Genomic DNA. Translation: EAW96133.1. BC063424 mRNA. Translation: AAH63424.1. BC126289 mRNA. Translation: AAI26290.1. BC126291 mRNA. Translation: AAI26292.1.
IPI	IPI00401793. IPI00401794. IPI00747901. IPI00879754. IPI00880140.
RefSeq	NP_001193939.1. NM_001207010.1. NP_612210.4. NM_138337.5. NP_963917.2. NM_201623.3.
UniGene	Hs.190519.
3D structure databases
ProteinModelPortal	Q5QGZ9.
SMR	Q5QGZ9. Positions 131-253.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5QGZ9.
PTM databases
PhosphoSite	Q5QGZ9.
Polymorphism databases
DMDM	308153619.
Proteomic databases
PRIDE	Q5QGZ9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355690; ENSP00000347916; ENSG00000172322.
GeneID	160364.
KEGG	hsa:160364.
UCSC	uc001qwq.1. human. uc001qws.2. human.
Organism-specific databases
CTD	160364.
GeneCards	GC12P010124.
HGNC	HGNC:31713. CLEC12A.
MIM	612088. gene.
neXtProt	NX_Q5QGZ9.
PharmGKB	PA142672094.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16137.
GeneTree	ENSGT00600000084307.
HOVERGEN	HBG107715.
OrthoDB	EOG40P47N.
PhylomeDB	Q5QGZ9.
Gene expression databases
ArrayExpress	Q5QGZ9.
Bgee	Q5QGZ9.
CleanEx	HS_CLEC12A.
Genevestigator	Q5QGZ9.
Family and domain databases
InterPro	IPR001304. C-type_lectin. IPR016186. C-type_lectin-like. IPR016187. C-type_lectin_fold. [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]
SUPFAM	SSF56436. C-type_lectin_fold. 1 hit.
PROSITE	PS00615. C_TYPE_LECTIN_1. False negative. PS50041. C_TYPE_LECTIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

CL12A_HUMAN

Accession

Primary (citable) accession number: Q5QGZ9
Secondary accession number(s): B2RA16 , Q6P4H1, Q6RH77, Q6RH78, Q8TDQ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	October 5, 2010
Last modified:	December 14, 2011
This is version 58 of the entry and version 3 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.