P12035 (K2C3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Keratin, type II cytoskeletal 3

Alternative name(s):
65 kDa cytokeratin
Cytokeratin-3
Short name=CK-3
Keratin-3
Short name=K3
Type-II keratin Kb3

Gene names

Name:

KRT3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	628 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Subunit structure	Heterotetramer of two type I and two type II keratins. Keratin-3 associates with keratin-12.
Tissue specificity	Cornea specific.
Involvement in disease	Corneal dystrophy, Meesmann (MECD) [MIM:122100]: An autosomal dominant corneal disease characterized by fragility of the anterior corneal epithelium. Patients are usually asymptomatic until adulthood when rupture of the corneal microcysts may cause erosions, producing clinical symptoms such as photophobia, contact lens intolerance and intermittent diminution of visual acuity. Rarely, subepithelial scarring causes irregular corneal astigmatism and permanent visual impairment. Histological examination shows a disorganized and thickened epithelium with widespread cytoplasmic vacuolation and numerous small, round, debris-laden intraepithelial cysts. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5
Miscellaneous	There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Sequence similarities	Belongs to the intermediate filament family.
Sequence caution	The sequence CAF31522.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Coding sequence diversity	Polymorphism
Disease	Corneal dystrophy Disease mutation
Domain	Coiled coil
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB intermediate filament cytoskeleton organization Inferred from mutant phenotype Ref.4. Source: UniProtKB
Cellular_component	keratin filament Traceable author statement Ref.4. Source: UniProtKB
Molecular_function	structural molecule activity Inferred from mutant phenotype Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 628	628	Keratin, type II cytoskeletal 3		PRO_0000063716
Regions
	Region	1 – 197	197	Head
	Region	198 – 509	312	Rod
	Region	198 – 233	36	Coil 1A
	Region	234 – 254	21	Linker 1
	Region	255 – 346	92	Coil 1B
	Region	347 – 370	24	Linker 12
	Region	371 – 509	139	Coil 2
	Region	510 – 628	119	Tail
	Compositional bias	10 – 169	160	Gly-rich
	Compositional bias	536 – 612	77	Gly-rich
Natural variations
	Natural variant	44	1	G → A. Corresponds to variant rs28721426 [ dbSNP | Ensembl ].		VAR_061297
	Natural variant	375	1	R → G. Ref.1 Corresponds to variant rs3887954 [ dbSNP | Ensembl ].		VAR_056023
	Natural variant	503	1	R → P in MECD. Ref.5 Corresponds to variant rs60410063 [ dbSNP | Ensembl ].		VAR_031327
	Natural variant	509	1	E → K in MECD. Ref.4 Corresponds to variant rs57872071 [ dbSNP | Ensembl ].		VAR_003868
Experimental info
	Sequence conflict	162	1	G → A in CAA28991. Ref.1
	Sequence conflict	175	1	I → T in CAA28991. Ref.1
	Sequence conflict	184	1	N → K in CAA28991. Ref.1
	Sequence conflict	187	1	I → T in CAA28991. Ref.1
	Sequence conflict	298	1	T → Y in CAA28993. Ref.1
	Sequence conflict	397	1	L → M in CAA28996. Ref.1
	Sequence conflict	409	1	D → G in CAF31522. Ref.3
	Sequence conflict	448	1	E → Q in CAA28996. Ref.1
	Sequence conflict	511	1	Y → YS in CAA28996. Ref.1
	Sequence conflict	562	1	S → I in CAA28996. Ref.1
	Sequence conflict	580	1	S → T in CAA28996. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P12035 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 65FDB8CAA7F3C960	FASTA	628	64,417
	10 20 30 40 50 60 MSRQASKTSG GGSQGFSGRS AVVSGSSRMS CVAHSGGAGG GAYGFRSGAG GFGSRSLYNL 70 80 90 100 110 120 GGNKSISISV AAGGSRAGGF GGGRSSCAFA GGYGGGFGSG YGGGFGGGFG GGRGMGGGFG 130 140 150 160 170 180 GAGGFGGAGG FGGAGGFGGP GGFGGSGGFG GPGSLGSPGG FGPGGFPGGI QEVTINQSLL 190 200 210 220 230 240 QPLNVEIDPQ IGQVKAQERE QIKTLNNKFA SFIDKVRFLE QQNKVLETKW NLLQQQGTSS 250 260 270 280 290 300 ISGTNNLEPL FENHINYLRS YLDNILGERG RLDSELKNME DLVEDFKKKY EDEINKRTAA 310 320 330 340 350 360 ENEFVTLKKD VDSAYMNKVE LQAKVDALID EIDFLRTLYD AELSQMQSHI SDTSVVLSMD 370 380 390 400 410 420 NNRSLDLDSI IAEVRAQYED IAQRSKAEAE ALYQTKLGEL QTTAGRHGDD LRNTKSEIIE 430 440 450 460 470 480 LNRMIQRLRA EIEGVKKQNA NLQTAIAEAE QHGEMALKDA NAKLQELQAA LQQAKDDLAR 490 500 510 520 530 540 LLRDYQELMN VKLALDVEIA TYRKLLEGEE YRMSGECPSA VSISVVSSST TSASAGGYGG 550 560 570 580 590 600 GYGGGMGGGL GGGFSAGGGS GSGFGRGGGG GIGGGFGGGS SGFSGGSGFG SISGARYGVS 610 620 GGGFSSASNR GGSIKFSQSS QSSQRYSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evolution of keratin genes: different protein domains evolve by different pathways." Klinge E.M., Sylvestre Y.R., Freedberg I.M., Blumenberg M. J. Mol. Evol. 24:319-329(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-375.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Characterization of new members of the human type II keratin gene family and a general evaluation of the keratin gene domain on chromosome 12q13.13." Rogers M.A., Edler L., Winter H., Langbein L., Beckmann I., Schweizer J. J. Invest. Dermatol. 124:536-544(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-628. Tissue: Eye.
[4]	"Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy." Irvine A.D., Corden L.D., Swensson O., Swensson B., Moore J.E., Frazer D.G., Smith F.J.D., Knowlton R.G., Christophers E., Rochels R., Uitto J., McLean W.H.I. Nat. Genet. 16:184-187(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MECD LYS-509.
[5]	"Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 Taiwanese families with Meesmann corneal dystrophy." Chen Y.T., Tseng S.H., Chao S.C. Cornea 24:928-932(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MECD PRO-503.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

Wikipedia

Keratin-3 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	X05418 Genomic DNA. Translation: CAA28991.1. X05419 Genomic DNA. Translation: CAA28992.1. X05420 Genomic DNA. Translation: CAA28993.1. X05420 Genomic DNA. Translation: CAA28994.1. X05420 Genomic DNA. Translation: CAA28995.1. X05421 Genomic DNA. Translation: CAA28996.1. AC107016 Genomic DNA. No translation available. AJ628418 mRNA. Translation: CAF31522.1. Different initiation.
IPI	IPI00290857.
PIR	A29666.
RefSeq	NP_476429.2. NM_057088.2.
UniGene	Hs.680652.
3D structure databases
ProteinModelPortal	P12035.
SMR	P12035. Positions 198-339, 366-508.
ModBase	Search...
Protein-protein interaction databases
IntAct	P12035. 3 interactions.
STRING	9606.ENSP00000413479.
PTM databases
PhosphoSite	P12035.
Polymorphism databases
DMDM	81175179.
Proteomic databases
PaxDb	P12035.
PRIDE	P12035.
Protocols and materials databases
DNASU	3850.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000417996; ENSP00000413479; ENSG00000186442.
GeneID	3850.
KEGG	hsa:3850.
UCSC	uc001say.3. human.
Organism-specific databases
CTD	3850.
GeneCards	GC12M053183.
H-InvDB	HIX0036742.
HGNC	HGNC:6440. KRT3.
MIM	122100. phenotype. 148043. gene.
neXtProt	NX_P12035.
Orphanet	98954. Meesmann corneal dystrophy.
PharmGKB	PA30228.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG146968.
HOGENOM	HOG000230976.
HOVERGEN	HBG013015.
InParanoid	P12035.
KO	K07605.
PhylomeDB	P12035.
Gene expression databases
Bgee	P12035.
CleanEx	HS_KRT3.
Genevestigator	P12035.
GermOnline	ENSG00000186442. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR018039. Intermediate_filament_CS. IPR003054. Keratin_II. [Graphical view]
PANTHER	PTHR23239. PTHR23239. 1 hit. PTHR23239:SF18. PTHR23239:SF18. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01276. TYPE2KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3850.
NextBio	15149.
SOURCE	Search...

Entry information

Entry name

K2C3_HUMAN

Accession

Primary (citable) accession number: P12035
Secondary accession number(s): A6NIS2, Q701L8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 130 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.