SwissPalm

Protein general information from UniProt

Protein names

Collagen alpha-2; IV chain [Cleaved into: Canstatin]

Subcellular location

Secreted (By similarity); basement membrane (Potential); extracellular space (Probable); extracellular matrix (Probable)

Isoforms & protein length

Isoform 1 (main): 1707 aa

Known functions

Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins (By similarity). Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens. Proteolytic processing produces the C-terminal NC1 peptide, canstatin. The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues. Belongs to the type IV collagen family.

Cross-references

Source	Identifiers
UniProt gene names	Col4a2
UniProt secondary AC	Q91VI3, Q8BPK3, Q8BPI9, Q6U9X1, Q6RCT7, Q6RCT6, Q66JS5, Q61375, Q3TPV9, Q3B7C2
Refseq protein ID	NP_034062.3
IPI ID	IPI00129573, IPI00266676, IPI00405886, IPI00338452

Source	Identifiers
Ensembl protein	ENSMUSP00000033899
Ensembl gene	ENSMUSG00000031503
MGI ID	MGI:88455

Copy in clipboard UniProt feature viewer

Isoform sequence alignment

Tip: Hover over an amino acid to display its position!

Orthologs

Select all Deselect all

UniProt AC	UniProt ID	Orthology source	Organism	Gene names	Protein name	Palmitome articles	Techniques	Sites	Predicted
P08572	CO4A2_HUMAN	OrthoDB, Ensembl, InParanoid, MetaPhors	H. sapiens	COL4A2	Collagen alpha-2	1/17	1	1	Yes
F1M6Q3	F1M6Q3_RAT	InParanoid	R. norvegicus	Col4a2	Collagen type IV alpha 2 chain	0/2	0	0	No
F1LRJ1	F1LRJ1_RAT	OrthoDB	R. norvegicus	LOC100911572, Col4a3	Collagen type IV alpha 3 chain	0/2	0	0	Yes

Ortholog sequence alignment (CLUSTALW)

Sites (from validation or large-scale experiments)

Isoforms	Position	Probability	Studies	Techniques
P08122	1653	NA	SPalmE:855 Shen LF et al. (2017)*	ARAC

Cysteine summary and predictions

Pos in alignment	42	47	51	53	137	481	483	656	676	1499	1532	1544	1550	1585
Subcell. location	E	E	E	E	E	E	E	E	E	E	E	E	E	E
Disulfide	no	no	no	no	no	no	no	no	no	no	no	no	no	no
PSIPRED v.3.5 prediction	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
UniProt secondary structure	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Pos in isoform 1 [Main] CSS-Palm 4.0 PalmPred	Cys⁴²	Cys⁴⁷ HC	Cys⁵¹	Cys⁵³	Cys¹³⁷	Cys⁴⁸¹	Cys⁴⁸³	Cys⁶⁵⁶	Cys⁶⁷⁶	Cys¹⁴⁹⁹	Cys¹⁵³²	Cys¹⁵⁴⁴	Cys¹⁵⁵⁰	Cys¹⁵⁸⁵

Pos in alignment	1588	1607	1641	1653	1660	1700	1703
Subcell. location	E	E	E	E	E	E	E
Disulfide	no	no	no	no	no	no	no
PSIPRED v.3.5 prediction	NA	NA	NA	NA	NA	NA	NA
UniProt secondary structure	NA	NA	NA	NA	NA	NA	NA
Pos in isoform 1 [Main] CSS-Palm 4.0 PalmPred	Cys¹⁵⁸⁸	Cys¹⁶⁰⁷	Cys¹⁶⁴¹	Cys¹⁶⁵³	Cys¹⁶⁶⁰	Cys¹⁷⁰⁰ MC	Cys¹⁷⁰³ MC

Legend

Subcell. location

U Undefined E Extracellular/Lumenal T Transmembrane C Cytosolic/Nuclear

Prediction confidence

Cysteine position: Predicted (high confidence prediction with CSS-Palm or/and PalmPred) and validated (in terms of disulfide bonds and cellular location) / Predicted but not validated (in terms of disulfide bond and cellular location) / Not predicted
CSS-Palm 4.0: High confidence, Medium confidence, Low confidence, Not predicted.
PalmPred: High confidence (score > 0.4), Medium confidence (0.1 < score < 0.4), Low confidence (score < 0.1), Not predicted.

Palmitoyl-proteome experiments

List of palmitoyl-proteomes

Tip: Keep CTRL key pressed down while clicking on column headers to do multiple sorting. This applies to any sortable table on this site.

ID of the experiment	Reference	Year	Organism	Cell type	Subcellular location	Technique(s)	Found?	In list	All lists
SPalmE:14	Roth AF et al.	2006	Saccharomyces cerevisiae	Isogenic LRB759	Total membrane	ABE	x		HC HC: 48 hits
SPalmE:13	Kang R et al.	2008	Rattus norvegicus	Cortical neuron	Synaptosomal membrane	ABE	x		HC: 107 hits LC: 308 hits
SPalmE:6	Martin BR et al.	2009	Homo sapiens	Jurkat	Total membrane	Click chemistry	x		HC: 127 hits LC: 188 hits List: 0 hits
SPalmE:577	Yang W et al.	2010	Homo sapiens	DU145	Non-lipid raft	ABE	x		HC: 63 hits LC: 147 hits
SPalmE:1	Yang W et al.	2010	Homo sapiens	DU145	Total membrane	ABE	x		HC: 162 hits LC: 218 hits
SPalmE:578	Yang W et al.	2010	Homo sapiens	DU145	Lipid raft	ABE	x		HC: 102 hits LC: 73 hits
SPalmE:10	Yount JS et al.	2010	Mus musculus	Dendritic cell	Total cell lysate	Click chemistry	x		HC: 59 hits LC: 105 hits
SPalmE:2	Dowal L et al.	2011	Homo sapiens	Platelet	Total membrane	ABE	x		List: 214 hits
SPalmE:511	Emmer BT et al.	2011	Trypanosoma brucei brucei	NA	Total cell lysate	ABE	x		List: 126 hits
SPalmE:8	Merrick BA et al.	2011	Mus musculus	Macrophage Raw 264.7	Total membrane	ABE	x		List: 69 hits
SPalmE:12	Martin BR et al.	2011	Mus musculus	BW5147-derived mouse T-cell hybridoma cell	Total membrane	Click chemistry	x		HC HC: 352 hits LC LC: 8 hits
SPalmE:5	Forrester MT et al.	2011	Homo sapiens	HEK293	Total membrane	ARAC	Ortholog	in List [CO4A2]	List: 69 hits
SPalmE:7	Wilson JP et al.	2011	Homo sapiens	Jurkat	Total cell lysate	Click chemistry	x		HC: 164 hits LC: 178 hits
SPalmE:162	Jones ML et al.	2012	Plasmodium falciparum	Whole organism	Total cell lysate	ABE	x		HC: 100 hits LC: 217 hits
SPalmE:580	Jones ML et al.	2012	Plasmodium falciparum	Whole organism	Total cell lysate	Click chemistry, SILAC	x		HC: 79 hits LC: 89 hits
SPalmE:3	Ivaldi C et al.	2012	Homo sapiens	B-cell	Total membrane	ABE	x		HC HC: 93 hits
SPalmE:11	Li Y et al.	2012	Mus musculus	Neural stem cell	Total cell lysate	Click chemistry	x		HC HC: 254 hits
SPalmE:4	Marin EP et al.	2012	Homo sapiens	Umbilical vein blood	NA	ABE	x		List: 154 hits
SPalmE:160	Zhang MM et al.	2013	Schizosaccharomyces pombe	Whole organism	Total cell lysate	Click chemistry	x		List: 238 hits
SPalmE:119	Wan J et al.	2013	Mus musculus	Brain	Total cell lysate	ABE	x		List: 378 hits
SPalmE:15	Hemsley PA et al.	2013	Arabidopsis thaliana	Heyn Col-4 ecotype root cell suspension	Microsomal membrane	ABE	x		HC: 122 hits MC: 94 hits LC: 366 hits
SPalmE:9	Ren W et al.	2013	Mus musculus	3T3-L1 and epididymal fat pads	Total membrane	ARAC	x		List: 664 hits
SPalmE:184	Wei X et al.	2014	Homo sapiens	HUVEC	Total cell lysate	ABE	x		Palm decreased: 40 hits Palm increased: 33 hits List: 367 hits
SPalmE:508	Chesarino NM et al.	2014	Mus musculus	MEF	Total cell lysate	Click chemistry	x		List: 436 hits
SPalmE:507	Chesarino NM et al.	2014	Mus musculus	DC2.4	Total cell lysate	Click chemistry	x		List: 246 hits
SPalmE:510	Santiago-Tirado FH et al.	2015	Cryptococcus neoformans	NA	Total cell lysate	Click chemistry	x		List: 354 hits
SPalmE:506	Morrison E et al.	2015	Homo sapiens	Jurkat	Total cell lysate	Click chemistry, SILAC	x		List: 226 hits
SPalmE:536	Foe IT et al.	2015	Toxoplasma gondii	NA	Total membrane	Click chemistry	x		HC: 210 hits MC: 72 hits
SPalmE:619	Peng T et al.	2015	Homo sapiens	HEK293	Total cell lysate	Alk16 Labeling	x		List: 354 hits
SPalmE:620	Peng T et al.	2015	Homo sapiens	HEK293	Total cell lysate	Photo cleavable x-alk16 labeling	x		List: 354 hits
SPalmE:509	Santiago-Tirado FH et al.	2015	Cryptococcus neoformans	NA	Total cell lysate	Click chemistry	x		List: 426 hits
SPalmE:504	Serwa RA et al.	2015	Homo sapiens	RPE-1	Total cell lysate	16-HDYA labeling, SILAC	x		List: 1348 hits
SPalmE:540	Gould NS et al.	2015	Mus musculus	Liver	Total cell lysate	APE	x		List: 780 hits
SPalmE:529	Colquhoun DR et al.	2015	Homo sapiens	174 x CEM.T1	Total cell lysate	Click-IT Palmitic Acid labeling	x		List: 113 hits
SPalmE:505	Morrison E et al.	2015	Homo sapiens	Primary CD4 + T cells	Total cell lysate	ABE, In gel SILAC labeling	x		List: 274 hits
SPalmE:723	Hernandez JL et al.	2016	Homo sapiens	MCF7	Total cell lysate	Alk16 Labeling	x		List: 1353 hits
SPalmE:698	Pinner AL et al.	2016	Homo sapiens	Brain	Total cell lysate	ABE	x		List: 216 hits
SPalmE:724	Fang C et al.	2016	Homo sapiens	SW480	NA	ARAC	x		List: 100 hits
SPalmE:902	Caballero MC et al.	2016	Toxoplasma gondii	whole parasite lysates	NA	ABE	x		HC: 164 hits
SPalmE:829	Upadhyay S et al.	2016	Aspergillus fumigatus	Conidia	NA	ABE	x		List: 133 hits
SPalmE:909	Thinon E et al.	2016	Mus musculus	Macrophage Raw 264.7	Total cell lysate	Alk16 Labeling	x		HC: 197 hits MC: 143 hits LC: 302 hits
SPalmE:903	Collins MO et al.	2017	Mus musculus	Forebrain	NA	ABE	x		HC: 1079 hits
SPalmE:906	Edmonds MJ et al.	2017	Rattus norvegicus	Brain	NA	ABE	x		List: 193 hits
SPalmE:993	Shen LF et al.	2017	Mus musculus	Liver	Total membrane	ARAC	x		ZDHHC13 substrates: 16 hits
SPalmE:907	Edmonds MJ et al.	2017	Rattus norvegicus	Brain	NA	ARAC	x		List: 95 hits
SPalmE:855	Shen LF et al.	2017	Mus musculus	Liver	Total membrane	ARAC	Found	in List	List: 865 hits
SPalmE:908	Sobocińska J et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	Click chemistry	x		Palm. up with LPS: 156 hits Palm. down with LPS: 189 hits
SPalmE:919	Sobocińska J et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	Click chemistry	x		List: 646 hits
SPalmE:920	Sobocińska J et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	Click chemistry	x		LPS treatment: 646 hits
SPalmE:1186	Thinon E et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	Alk16 Labeling, NH2OH cleavage of thioester bond	x		HC: 177 hits MC: 162 hits LC: 123 hits
SPalmE:1187	Thinon E et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	ARAC	x		HC: 281 hits MC: 139 hits LC: 113 hits
SPalmE:1183	Thinon E et al.	2018	Homo sapiens	HeLa	Total cell lysate	Alk16 Labeling, NH2OH cleavage of thioester bond	x		HC: 132 hits MC: 138 hits LC: 110 hits
SPalmE:1184	Thinon E et al.	2018	Homo sapiens	HeLa	Total cell lysate	ARAC	x		HC: 545 hits MC: 415 hits LC: 219 hits
SPalmE:1185	Thinon E et al.	2018	Homo sapiens	HeLa	Total cell lysate	Alk16 Labeling, NH2OH cleavage of thioester bond, LC-MS	x		Chymotrypsin: 286 hits Trypsin: 1291 hits
SPalmE:1181	Thinon E et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	Alk16 Labeling, NH2OH cleavage of thioester bond	x		HC: 244 hits MC: 187 hits LC: 120 hits
SPalmE:1182	Thinon E et al.	2018	Mus musculus	Macrophage Raw 264.7	Total cell lysate	ARAC	x		HC: 198 hits MC: 143 hits LC: 120 hits
SPalmE:1191	Won SJ et al.	2018	Homo sapiens	HEK293T	Total cell lysate	Click chemistry	x		List: 195 hits
SPalmE:1192	Won SJ et al.	2018	Homo sapiens	HAP1	Total cell lysate	Click chemistry	x		List: 984 hits
SPalmE:1193	Won SJ et al.	2018	Homo sapiens	HAP1	Total cell lysate	ARAC	x		List: 1394 hits
SPalmE:1194	Won SJ et al.	2018	Homo sapiens	HAP1	Total cell lysate	ARAC,	x		List: 1404 hits
SPalmE:1203	Zhang X et al.	2018	Mus musculus	Brain	Total membrane	Enrichment by magnetic nanoparticles	x		HC: 917 hits MC: 352 hits LC: 15 hits

Summary table by organism

Organism	Total number of palmitoyl-proteome articles	Total number of palmitoyl-proteomes	Number of palmitoyl-proteomes containing this protein or an ortholog	% of palmitoyl-proteomes containing this protein or an ortholog	Orthologs
S. cerevisiae S288c	1	1	0	0.0	NA
R. norvegicus	2	3	0	0.0	NA
H. sapiens	17	26	1	3.8	CO4A2_HUMAN
M. musculus	14	21	1	4.8	NA
T. brucei brucei	1	1	0	0.0	NA
P. falciparum	1	2	0	0.0	NA
S. pombe	1	1	0	0.0	NA
A. thaliana	1	1	0	0.0	NA
C. neoformans var. grubii serotype A strain H99	1	2	0	0.0	NA
T. gondii	2	2	0	0.0	NA
A. fumigatus	1	1	0	0.0	NA

References

Authors	Year	Artile title	PMID
Wan J et al.	2013	Tracking brain palmitoylation change: predominance of glial change in a mouse model of Huntington's disease.	24211138
Edmonds MJ et al.	2017	Analysis of the brain palmitoyl-proteome using both acyl-biotin exchange and acyl-resin-assisted capture methods.	28607426
Collins MO et al.	2017	Global, site-specific analysis of neuronal protein S-acylation.	28680068
Shen LF et al.	2017	Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver.	28526873
Colquhoun DR et al.	2015	Bioorthogonal mimetics of palmitoyl-CoA and myristoyl-CoA and their subsequent isolation by click chemistry and characterization by mass spectrometry reveal novel acylated host-proteins modified by HIV-1 infection.	25914232
Sobocińska J et al.	2018	Lipopolysaccharide Upregulates Palmitoylated Enzymes of the Phosphatidylinositol Cycle: An Insight from Proteomic Studies.	29217618
Li Y et al.	2012	DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on induction of neuronal differentiation in cultured cells.	22081607
Thinon E et al.	2016	Bioorthogonal Chemical Reporters for Monitoring Unsaturated Fatty-Acylated Proteins.	27350074
Kang R et al.	2008	Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation.	19092927
Yang W et al.	2010	Proteome scale characterization of human S-acylated proteins in lipid raft-enriched and non-raft membranes.	19801377
Yount JS et al.	2010	Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3.	20601941
Santiago-Tirado FH et al.	2015	A Single Protein S-acyl Transferase Acts through Diverse Substrates to Determine Cryptococcal Morphology, Stress Tolerance, and Pathogenic Outcome.	25970403
Upadhyay S et al.	2016	Interactions between Melanin Enzymes and Their Atypical Recruitment to the Secretory Pathway by Palmitoylation.	27879337
Won SJ et al.	2018	Temporal Profiling Establishes a Dynamic S-Palmitoylation Cycle.	29733200
Wilson JP et al.	2011	Proteomic analysis of fatty-acylated proteins in mammalian cells with chemical reporters reveals S-acylation of histone H3 variants.	21076176
Pinner AL et al.	2016	Decreased protein S-palmitoylation in dorsolateral prefrontal cortex in schizophrenia.	26876311
Martin BR et al.	2011	Global profiling of dynamic protein palmitoylation.	22056678
Jones ML et al.	2012	Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.	22901544
Dowal L et al.	2011	Proteomic analysis of palmitoylated platelet proteins.	21813449
Foe IT et al.	2015	Global Analysis of Palmitoylated Proteins in Toxoplasma gondii.	26468752
Gould NS et al.	2015	Site-Specific Proteomic Mapping Identifies Selectively Modified Regulatory Cysteine Residues in Functionally Distinct Protein Networks.	26165157
Serwa RA et al.	2015	Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics.	26256475
Martin BR et al.	2009	Large-scale profiling of protein palmitoylation in mammalian cells.	19137006
Chesarino NM et al.	2014	Chemoproteomics reveals Toll-like receptor fatty acylation.	25371237
Hernandez JL et al.	2016	Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition.	27030425
Thinon E et al.	2018	Selective Enrichment and Direct Analysis of Protein S-Palmitoylation Sites.	29575903
Ivaldi C et al.	2012	Proteomic analysis of S-acylated proteins in human B cells reveals palmitoylation of the immune regulators CD20 and CD23.	22615937
Caballero MC et al.	2016	Identification of new palmitoylated proteins in Toxoplasma gondii.	26825284
Morrison E et al.	2015	Quantitative analysis of the human T cell palmitome.	26111759
Marin EP et al.	2012	Endothelial cell palmitoylproteomic identifies novel lipid-modified targets and potential substrates for protein acyl transferases.	22496122
Wei X et al.	2014	Insulin-regulated protein palmitoylation impacts endothelial cell function.	24357059
Merrick BA et al.	2011	Proteomic profiling of S-acylated macrophage proteins identifies a role for palmitoylation in mitochondrial targeting of phospholipid scramblase 3.	21785166
Emmer BT et al.	2011	Global analysis of protein palmitoylation in African trypanosomes.	21193548
Ren W et al.	2013	Proteomic analysis of protein palmitoylation in adipocytes.	23599907
Fang C et al.	2016	Identification of Palmitoylated Transitional Endoplasmic Reticulum ATPase by Proteomic Technique and Pan Antipalmitoylation Antibody.	26865113
Roth AF et al.	2006	Global analysis of protein palmitoylation in yeast.	16751107
Forrester MT et al.	2011	Site-specific analysis of protein S-acylation by resin-assisted capture.	21044946
Zhang MM et al.	2013	Quantitative control of protein S-palmitoylation regulates meiotic entry in fission yeast.	23843742
Zhang X et al.	2018	Ultradeep Palmitoylomics Enabled by Dithiodipyridine-Functionalized Magnetic Nanoparticles.	29660268
Peng T et al.	2015	Bifunctional fatty acid chemical reporter for analyzing S-palmitoylated membrane protein-protein interactions in mammalian cells.	25575299
Hemsley PA et al.	2013	A proteomic approach identifies many novel palmitoylated proteins in Arabidopsis.	23252521

P08122 CO4A2_MOUSE