Q13492 (PICAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol-binding clathrin assembly protein

Alternative name(s):
Clathrin assembly lymphoid myeloid leukemia protein

Gene names

Name:	PICALM
Synonyms:	CALM

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

General annotation (Comments)

Function	Assembly protein recruiting clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. May be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. Involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. Ref.5
Subunit structure	Binds clathrin; involves primarily the C-terminal sequences, but the full-length protein is required for full binding capacity. Binds phosphatidylinositol-4,5- bisphosphate.
Subcellular location	Membrane › clathrin-coated pit. Golgi apparatus. Cytoplasmic vesicle › clathrin-coated vesicle. Note: Colocalized with clathrin in the Golgi area. Ref.5
Tissue specificity	Expressed in all tissues examined. Ref.1
Involvement in disease	Note=A chromosomal aberration involving PICALM is found in diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with MLLT10.
Sequence similarities	Contains 1 ENTH (epsin N-terminal homology) domain.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Coated pit Cytoplasmic vesicle Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	clathrin coat assembly Inferred from mutant phenotype. Source: BHF-UCL endosome transport Inferred from mutant phenotype. Source: BHF-UCL negative regulation of receptor-mediated endocytosis Inferred from direct assay Ref.5. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: BHF-UCL receptor internalization Inferred from mutant phenotype. Source: BHF-UCL regulation of protein localization Inferred from direct assay Ref.5. Source: BHF-UCL
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell clathrin coat Inferred from electronic annotation. Source: InterPro clathrin-coated vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell coated pit Inferred from direct assay Ref.5. Source: UniProtKB nucleus Inferred from direct assay. Source: BHF-UCL postsynaptic membrane Inferred from sequence or structural similarity. Source: BHF-UCL presynaptic membrane Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	1-phosphatidylinositol binding Inferred from sequence or structural similarity. Source: UniProtKB clathrin heavy chain binding Inferred from direct assay Ref.5. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q13492-1)

Also known as: Type I;

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: Q13492-2)

Also known as: Type II;

The sequence of this isoform differs from the canonical sequence as follows:
     594-613: Missing.

Isoform 3 (identifier: Q13492-3)

The sequence of this isoform differs from the canonical sequence as follows:
     420-469: Missing.
     593-593: M → MNGMHFPQY

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 652	652	Phosphatidylinositol-binding clathrin assembly protein		PRO_0000187062
Regions
	Domain	14 – 145	132	ENTH
Sites
	Site	648 – 649	2	Breakpoint for translocation to form CALM/MLLT10 fusion protein
Natural variations
	Alternative sequence	420 – 469	50	Missing in isoform 3.		VSP_009607
	Alternative sequence	593	1	M → MNGMHFPQY in isoform 3.		VSP_009608
	Alternative sequence	594 – 613	20	Missing in isoform 2.		VSP_004067
	Natural variant	158	1	T → P. Corresponds to variant rs12800974 [ dbSNP | Ensembl ].		VAR_028191
	Natural variant	383	1	S → F. Corresponds to variant rs12222608 [ dbSNP | Ensembl ].		VAR_028192
	Natural variant	578	1	W → C. Ref.1 Ref.4 Corresponds to variant rs1043858 [ dbSNP | Ensembl ].		VAR_028193
	Natural variant	579	1	Q → E. Ref.1 Ref.4 Corresponds to variant rs1043859 [ dbSNP | Ensembl ].		VAR_028194
	Natural variant	641	1	F → L. Corresponds to variant rs556337 [ dbSNP | Ensembl ].		VAR_028195
Experimental info
	Sequence conflict	212	1	N → H in AAB07762. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Type I) [UniParc]. Last modified October 17, 2006. Version 2. Checksum: AC3227E9D32AFEDA	FASTA	652	70,755
	10 20 30 40 50 60 MSGQSLTDRI TAAQHSVTGS AVSKTVCKAT THEIMGPKKK HLDYLIQCTN EMNVNIPQLA 70 80 90 100 110 120 DSLFERTTNS SWVVVFKSLI TTHHLMVYGN ERFIQYLASR NTLFNLSNFL DKSGLQGYDM 130 140 150 160 170 180 STFIRRYSRY LNEKAVSYRQ VAFDFTKVKR GADGVMRTMN TEKLLKTVPI IQNQMDALLD 190 200 210 220 230 240 FNVNSNELTN GVINAAFMLL FKDAIRLFAA YNEGIINLLE KYFDMKKNQC KEGLDIYKKF 250 260 270 280 290 300 LTRMTRISEF LKVAEQVGID RGDIPDLSQA PSSLLDALEQ HLASLEGKKI KDSTAASRAT 310 320 330 340 350 360 TLSNAVSSLA STGLSLTKVD EREKQAALEE EQARLKALKE QRLKELAKKP HTSLTTAASP 370 380 390 400 410 420 VSTSAGGIMT APAIDIFSTP SSSNSTSKLP NDLLDLQQPT FHPSVHPMST ASQVASTWGD 430 440 450 460 470 480 PFSATVDAVD DAIPSLNPFL TKSSGDVHLS ISSDVSTFTT RTPTHEMFVG FTPSPVAQPH 490 500 510 520 530 540 PSAGLNVDFE SVFGNKSTNV IVDSGGFDEL GGLLKPTVAS QNQNLPVAKL PPSKLVSDDL 550 560 570 580 590 600 DSSLANLVGN LGIGNGTTKN DVNWSQPGEK KLTGGSNWQP KVAPTTAWNA ATMAPPVMAY 610 620 630 640 650 PATTPTGMIG YGIPPQMGSV PVMTQPTLIY SQPVMRPPNP FGPVSGAQIQ FM
	Isoform 2 (Type II) [UniParc]. Checksum: D13D4427A30EE4FD	FASTA	632	68,764
	10 20 30 40 50 60 MSGQSLTDRI TAAQHSVTGS AVSKTVCKAT THEIMGPKKK HLDYLIQCTN EMNVNIPQLA 70 80 90 100 110 120 DSLFERTTNS SWVVVFKSLI TTHHLMVYGN ERFIQYLASR NTLFNLSNFL DKSGLQGYDM 130 140 150 160 170 180 STFIRRYSRY LNEKAVSYRQ VAFDFTKVKR GADGVMRTMN TEKLLKTVPI IQNQMDALLD 190 200 210 220 230 240 FNVNSNELTN GVINAAFMLL FKDAIRLFAA YNEGIINLLE KYFDMKKNQC KEGLDIYKKF 250 260 270 280 290 300 LTRMTRISEF LKVAEQVGID RGDIPDLSQA PSSLLDALEQ HLASLEGKKI KDSTAASRAT 310 320 330 340 350 360 TLSNAVSSLA STGLSLTKVD EREKQAALEE EQARLKALKE QRLKELAKKP HTSLTTAASP 370 380 390 400 410 420 VSTSAGGIMT APAIDIFSTP SSSNSTSKLP NDLLDLQQPT FHPSVHPMST ASQVASTWGD 430 440 450 460 470 480 PFSATVDAVD DAIPSLNPFL TKSSGDVHLS ISSDVSTFTT RTPTHEMFVG FTPSPVAQPH 490 500 510 520 530 540 PSAGLNVDFE SVFGNKSTNV IVDSGGFDEL GGLLKPTVAS QNQNLPVAKL PPSKLVSDDL 550 560 570 580 590 600 DSSLANLVGN LGIGNGTTKN DVNWSQPGEK KLTGGSNWQP KVAPTTAWNA ATMPPQMGSV 610 620 630 PVMTQPTLIY SQPVMRPPNP FGPVSGAQIQ FM
	Isoform 3 [UniParc]. Checksum: 3B0D0AEB901CF85D	FASTA	610	66,393
	10 20 30 40 50 60 MSGQSLTDRI TAAQHSVTGS AVSKTVCKAT THEIMGPKKK HLDYLIQCTN EMNVNIPQLA 70 80 90 100 110 120 DSLFERTTNS SWVVVFKSLI TTHHLMVYGN ERFIQYLASR NTLFNLSNFL DKSGLQGYDM 130 140 150 160 170 180 STFIRRYSRY LNEKAVSYRQ VAFDFTKVKR GADGVMRTMN TEKLLKTVPI IQNQMDALLD 190 200 210 220 230 240 FNVNSNELTN GVINAAFMLL FKDAIRLFAA YNEGIINLLE KYFDMKKNQC KEGLDIYKKF 250 260 270 280 290 300 LTRMTRISEF LKVAEQVGID RGDIPDLSQA PSSLLDALEQ HLASLEGKKI KDSTAASRAT 310 320 330 340 350 360 TLSNAVSSLA STGLSLTKVD EREKQAALEE EQARLKALKE QRLKELAKKP HTSLTTAASP 370 380 390 400 410 420 VSTSAGGIMT APAIDIFSTP SSSNSTSKLP NDLLDLQQPT FHPSVHPMST ASQVASTWGG 430 440 450 460 470 480 FTPSPVAQPH PSAGLNVDFE SVFGNKSTNV IVDSGGFDEL GGLLKPTVAS QNQNLPVAKL 490 500 510 520 530 540 PPSKLVSDDL DSSLANLVGN LGIGNGTTKN DVNWSQPGEK KLTGGSNWQP KVAPTTAWNA 550 560 570 580 590 600 ATMNGMHFPQ YAPPVMAYPA TTPTGMIGYG IPPQMGSVPV MTQPTLIYSQ PVMRPPNPFG 610 PVSGAQIQFM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family." Dreyling M.H., Martinez-Climent J.A., Zheng M., Mao J., Rowley J.D., Bohlander S.K. Proc. Natl. Acad. Sci. U.S.A. 93:4804-4809(1996) [PubMed: 8643484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION, TISSUE SPECIFICITY, VARIANTS CYS-578 AND GLU-579.
[2]	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].
[3]	"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 1 AND 3). Tissue: PNS.
[4]	"Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-14;q14-q21) suggests a potential role for truncated AF10 polypeptides." Silliman C.C., McGavran L., Wei Q., Miller L.A., Li S., Hunger S.P. Leukemia 12:1404-1410(1998) [PubMed: 9737689] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 575-652 (ISOFORMS 1 AND 2), VARIANTS CYS-578 AND GLU-579. Tissue: Bone marrow.
[5]	"Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic." Tebar F., Bohlander S.K., Sorkin A. Mol. Biol. Cell 10:2687-2702(1999) [PubMed: 10436022] [Abstract] Cited for: FUNCTION, INTERACTION WITH CLATHRIN, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U45976 mRNA. Translation: AAB07762.1. CH471076 Genomic DNA. Translation: EAW75120.1. BC048259 mRNA. Translation: AAH48259.2. BC064357 mRNA. Translation: AAH64357.1. BC073961 mRNA. Translation: AAH73961.1. AF060939 mRNA. Translation: AAC16711.1. AF060940 mRNA. Translation: AAC16712.1.
IPI	IPI00216184. IPI00290738. IPI00400849.
RefSeq	NP_001008660.1. NM_001008660.2. NP_001193875.1. NM_001206946.1. NP_001193876.1. NM_001206947.1. NP_009097.2. NM_007166.3.
UniGene	Hs.163893.
3D structure databases
ProteinModelPortal	Q13492.
SMR	Q13492. Positions 19-281.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13492. 5 interactions.
MINT	MINT-1636298.
STRING	Q13492.
PTM databases
PhosphoSite	Q13492.
Polymorphism databases
DMDM	116242714.
Proteomic databases
PRIDE	Q13492.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000341783; ENSP00000342095; ENSG00000073921. ENST00000447890; ENSP00000396321; ENSG00000073921.
GeneID	8301.
KEGG	hsa:8301.
UCSC	uc001pbm.1. human.
Organism-specific databases
CTD	8301.
GeneCards	GC11M085668.
H-InvDB	HIX0026132.
HGNC	HGNC:15514. PICALM.
HPA	HPA019053. HPA019061.
MIM	603025. gene.
neXtProt	NX_Q13492.
PharmGKB	PA33287.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04656.
HOVERGEN	HBG049391.
OrthoDB	EOG4C87RV.
PhylomeDB	Q13492.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	Q13492.
Bgee	Q13492.
CleanEx	HS_PICALM.
Genevestigator	Q13492.
GermOnline	ENSG00000073921. Homo sapiens.
Family and domain databases
InterPro	IPR011417. ANTH. IPR014712. Clathrin_Pinositid-bd_GAT-like. IPR008942. ENTH_VHS. IPR013809. Epsin-like_N. [Graphical view]
Gene3D	G3DSA:1.25.40.90. ENTH_VHS. 1 hit. G3DSA:1.20.58.150. Pinositid-bd_clathrin_GAT-like. 1 hit.
Pfam	PF07651. ANTH. 1 hit. [Graphical view]
SMART	SM00273. ENTH. 1 hit. [Graphical view]
SUPFAM	SSF48464. ENTH_VHS. 1 hit.
PROSITE	PS50942. ENTH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	31101.
PMAP-CutDB	Q13492.
SOURCE	Search...

Entry information

Entry name

PICAL_HUMAN

Accession

Primary (citable) accession number: Q13492
Secondary accession number(s): O60700, Q6GMQ6, Q86XZ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 107 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.